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FDA Approves New Esophageal Cancer Drug
The US Food and Drug Administration (FDA) has approved tislelizumab-jsgr (Tevimbra, BeiGene Ltd.) as second-line monotherapy for certain adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC).
Specifically, the novel checkpoint inhibitor is approved for patients with ESCC after prior systemic chemotherapy that did not include a programmed death–ligand 1 (PD-L1) inhibitor.
Approval was based on findings from the open-label, phase 3 RATIONALE 302 trial showing a statistically significant and clinically meaningful overall survival benefit with tislelizumab vs investigator’s choice of chemotherapy.
Study participants included 512 adults enrolled at 123 research sites in 11 countries in Europe, Asia, and North America. Patients were randomly assigned to receive intravenous tislelizumab, a humanized immunoglobulin G4 anti-programmed cell death protein 1 monoclonal antibody, at a dose of 200 mg every 3 weeks or investigator’s choice of standard chemotherapy with paclitaxel, docetaxel, or irinotecan until disease progression, unacceptable toxicity, or study withdrawal.
Median overall survival in the intention-to-treat population, the primary study endpoint, was 8.6 months vs 6.3 months in the chemotherapy arms (hazard ratio [HR], 0.70). The survival benefit was observed across predefined subgroups, including baseline PD-L1 status and region. The new agent was also associated with improved overall response rate (20.4% vs 9.8%) and more durable response (median duration of response of 7.1 vs 4.0 months; HR, 0.42) compared with chemotherapy.
The most common adverse reactions for tislelizumab, each occurring in at least 20% of treated patients, included increased glucose and decreased hemoglobin, lymphocytes, sodium, and albumin as well as increased alkaline phosphatase, anemia, fatigue, increased aspartate aminotransferase, musculoskeletal pain, decreased weight, increased alanine aminotransferase, and cough.
Fewer patients in the tislelizumab arm experienced grade 3 or greater treatment-emergent adverse events compared with the chemotherapy arm (46% vs 68%, respectively), and fewer patients discontinued tislelizumab vs chemotherapy due to such an event (7% vs 14%).
“Patients diagnosed with advanced or metastasized ESCC, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” Syma Iqbal, MD, of the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, stated in the BeiGene release. “The RATIONALE 302 trial showed that patients with previously treated ESCC who received Tevimbra saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.”
The approval, which was deferred in 2022 due to COVID-19-related restrictions, marks the first for the agent in the United States. Tislelizumab should be available in the United States in the second half of 2024, BeiGene noted.
The FDA is also reviewing a Biologics License Application for the agent as a first-line treatment for patients with unresectable, locally advanced, or metastatic ESCC and for those with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, BeiGene announced in a press release.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved tislelizumab-jsgr (Tevimbra, BeiGene Ltd.) as second-line monotherapy for certain adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC).
Specifically, the novel checkpoint inhibitor is approved for patients with ESCC after prior systemic chemotherapy that did not include a programmed death–ligand 1 (PD-L1) inhibitor.
Approval was based on findings from the open-label, phase 3 RATIONALE 302 trial showing a statistically significant and clinically meaningful overall survival benefit with tislelizumab vs investigator’s choice of chemotherapy.
Study participants included 512 adults enrolled at 123 research sites in 11 countries in Europe, Asia, and North America. Patients were randomly assigned to receive intravenous tislelizumab, a humanized immunoglobulin G4 anti-programmed cell death protein 1 monoclonal antibody, at a dose of 200 mg every 3 weeks or investigator’s choice of standard chemotherapy with paclitaxel, docetaxel, or irinotecan until disease progression, unacceptable toxicity, or study withdrawal.
Median overall survival in the intention-to-treat population, the primary study endpoint, was 8.6 months vs 6.3 months in the chemotherapy arms (hazard ratio [HR], 0.70). The survival benefit was observed across predefined subgroups, including baseline PD-L1 status and region. The new agent was also associated with improved overall response rate (20.4% vs 9.8%) and more durable response (median duration of response of 7.1 vs 4.0 months; HR, 0.42) compared with chemotherapy.
The most common adverse reactions for tislelizumab, each occurring in at least 20% of treated patients, included increased glucose and decreased hemoglobin, lymphocytes, sodium, and albumin as well as increased alkaline phosphatase, anemia, fatigue, increased aspartate aminotransferase, musculoskeletal pain, decreased weight, increased alanine aminotransferase, and cough.
Fewer patients in the tislelizumab arm experienced grade 3 or greater treatment-emergent adverse events compared with the chemotherapy arm (46% vs 68%, respectively), and fewer patients discontinued tislelizumab vs chemotherapy due to such an event (7% vs 14%).
“Patients diagnosed with advanced or metastasized ESCC, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” Syma Iqbal, MD, of the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, stated in the BeiGene release. “The RATIONALE 302 trial showed that patients with previously treated ESCC who received Tevimbra saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.”
The approval, which was deferred in 2022 due to COVID-19-related restrictions, marks the first for the agent in the United States. Tislelizumab should be available in the United States in the second half of 2024, BeiGene noted.
The FDA is also reviewing a Biologics License Application for the agent as a first-line treatment for patients with unresectable, locally advanced, or metastatic ESCC and for those with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, BeiGene announced in a press release.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved tislelizumab-jsgr (Tevimbra, BeiGene Ltd.) as second-line monotherapy for certain adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC).
Specifically, the novel checkpoint inhibitor is approved for patients with ESCC after prior systemic chemotherapy that did not include a programmed death–ligand 1 (PD-L1) inhibitor.
Approval was based on findings from the open-label, phase 3 RATIONALE 302 trial showing a statistically significant and clinically meaningful overall survival benefit with tislelizumab vs investigator’s choice of chemotherapy.
Study participants included 512 adults enrolled at 123 research sites in 11 countries in Europe, Asia, and North America. Patients were randomly assigned to receive intravenous tislelizumab, a humanized immunoglobulin G4 anti-programmed cell death protein 1 monoclonal antibody, at a dose of 200 mg every 3 weeks or investigator’s choice of standard chemotherapy with paclitaxel, docetaxel, or irinotecan until disease progression, unacceptable toxicity, or study withdrawal.
Median overall survival in the intention-to-treat population, the primary study endpoint, was 8.6 months vs 6.3 months in the chemotherapy arms (hazard ratio [HR], 0.70). The survival benefit was observed across predefined subgroups, including baseline PD-L1 status and region. The new agent was also associated with improved overall response rate (20.4% vs 9.8%) and more durable response (median duration of response of 7.1 vs 4.0 months; HR, 0.42) compared with chemotherapy.
The most common adverse reactions for tislelizumab, each occurring in at least 20% of treated patients, included increased glucose and decreased hemoglobin, lymphocytes, sodium, and albumin as well as increased alkaline phosphatase, anemia, fatigue, increased aspartate aminotransferase, musculoskeletal pain, decreased weight, increased alanine aminotransferase, and cough.
Fewer patients in the tislelizumab arm experienced grade 3 or greater treatment-emergent adverse events compared with the chemotherapy arm (46% vs 68%, respectively), and fewer patients discontinued tislelizumab vs chemotherapy due to such an event (7% vs 14%).
“Patients diagnosed with advanced or metastasized ESCC, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” Syma Iqbal, MD, of the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, stated in the BeiGene release. “The RATIONALE 302 trial showed that patients with previously treated ESCC who received Tevimbra saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.”
The approval, which was deferred in 2022 due to COVID-19-related restrictions, marks the first for the agent in the United States. Tislelizumab should be available in the United States in the second half of 2024, BeiGene noted.
The FDA is also reviewing a Biologics License Application for the agent as a first-line treatment for patients with unresectable, locally advanced, or metastatic ESCC and for those with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, BeiGene announced in a press release.
A version of this article appeared on Medscape.com.
An Easy, Effective Solution to Exercise-Induced Heat Sensitivity in RRMS?
WEST PALM BEACH, CALIFORNIA — , results from a new phase 3 trial suggested.
The findings from the randomized, placebo-controlled, double-blind study could solve this common problem, known clinically as Uhthoff’s phenomenon, that causes temporary worsening of MS symptoms with heat exposure.
“This could be a game changer,” said study investigator Victoria M. Leavitt, PhD, assistant professor of neuropsychology of Columbia University Irving Medical Center in New York City.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and published online in the Journal of Neurology.
A Common Condition
Research suggested that 60%-80% of MS patients experience heat sensitivity. However, while the exact cause is unknown, some evidence suggested it may be related to hypothalamic dysregulation or lesions of the hypothalamus.
Researchers have explored cooling strategies such as liquid-cooled clothing, but available tools can be hard to find, expensive, and cumbersome. Although aspirin has been linked to some symptom improvement in MS, its utility and that of acetaminophen for the condition has not been studied, Dr. Leavitt said.
For the single-center study, researchers recruited 60 patients (81% female; average age, 42 years; 73% White individuals) between 2019 and 2022. Overall, 37 completed at least one study visit, and 29 completed two to three visits. The average disease duration was 6 years.
Participants received oral administration of 650 mg aspirin, acetaminophen, or placebo at each of three study visits over 3 weeks, separated by at least 1 week. At each visit, they took part in a maximal exercise test conducted on a cycle ergometer and were asked to cycle at 50-60 revolutions/min for as long as possible.
Compared with placebo, body temperature increase from baseline to exercise stoppage was significantly reduced with aspirin (0.006 °F vs 0.68 °F; P < .001) and with acetaminophen (0.31 °F vs 0.68 °F; P < .004)
Neither medication was associated with a significant difference in time to exhaustion, and there were no serious adverse events.
“This is really nice because some people might have an adverse reaction to aspirin,” such as gastrointestinal issues. Acetaminophen has a different side-effect profile,” Dr. Leavitt said.
Both medications are inexpensive and available over the counter. The 650-mg acetaminophen dose used in the study is available in an extended-release formula. Typically aspirin isn’t available in doses larger than 325 mg. The 650-mg dose used in the study is considered safe but large.
Dr. Leavitt said she would like to study daily aspirin in people with MS to see if it can boost physical activity. “That’s the test of whether this will meaningfully affect the lives of people with MS,” she said.
No Harm From Overheating
Commenting on the findings, Katherine Knox, MD, associate professor of physical medicine and rehabilitation at the University of Saskatchewan, Canada, noted that “the intervention maybe be initially helpful for the person fearful of getting weaker when they get ‘hot’ with exercise.”
Dr. Knox, who wasn’t involved in the research, added that it’s important for patients with MS to overcome initial barriers and fears about exercise.
“However, for most people the effects of being warm with exercise are less concerning for them after education that the weakness is temporary and does not cause harm if one takes the right precautions such as planning ahead to avoid a fall,” she said. Also, inexpensive interventions such as a fan or a wet cotton headband can be helpful, she said.
The study “provides further evidence that the ‘overheating’ is not causing harm since the time to exhaustion was unchanged,” Dr. Knox added.
The study was funded by the National Institutes of Health. The authors had no disclosures. Disclosure information for Dr. Knox was not available.
A version of this article appeared on Medscape.com.
WEST PALM BEACH, CALIFORNIA — , results from a new phase 3 trial suggested.
The findings from the randomized, placebo-controlled, double-blind study could solve this common problem, known clinically as Uhthoff’s phenomenon, that causes temporary worsening of MS symptoms with heat exposure.
“This could be a game changer,” said study investigator Victoria M. Leavitt, PhD, assistant professor of neuropsychology of Columbia University Irving Medical Center in New York City.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and published online in the Journal of Neurology.
A Common Condition
Research suggested that 60%-80% of MS patients experience heat sensitivity. However, while the exact cause is unknown, some evidence suggested it may be related to hypothalamic dysregulation or lesions of the hypothalamus.
Researchers have explored cooling strategies such as liquid-cooled clothing, but available tools can be hard to find, expensive, and cumbersome. Although aspirin has been linked to some symptom improvement in MS, its utility and that of acetaminophen for the condition has not been studied, Dr. Leavitt said.
For the single-center study, researchers recruited 60 patients (81% female; average age, 42 years; 73% White individuals) between 2019 and 2022. Overall, 37 completed at least one study visit, and 29 completed two to three visits. The average disease duration was 6 years.
Participants received oral administration of 650 mg aspirin, acetaminophen, or placebo at each of three study visits over 3 weeks, separated by at least 1 week. At each visit, they took part in a maximal exercise test conducted on a cycle ergometer and were asked to cycle at 50-60 revolutions/min for as long as possible.
Compared with placebo, body temperature increase from baseline to exercise stoppage was significantly reduced with aspirin (0.006 °F vs 0.68 °F; P < .001) and with acetaminophen (0.31 °F vs 0.68 °F; P < .004)
Neither medication was associated with a significant difference in time to exhaustion, and there were no serious adverse events.
“This is really nice because some people might have an adverse reaction to aspirin,” such as gastrointestinal issues. Acetaminophen has a different side-effect profile,” Dr. Leavitt said.
Both medications are inexpensive and available over the counter. The 650-mg acetaminophen dose used in the study is available in an extended-release formula. Typically aspirin isn’t available in doses larger than 325 mg. The 650-mg dose used in the study is considered safe but large.
Dr. Leavitt said she would like to study daily aspirin in people with MS to see if it can boost physical activity. “That’s the test of whether this will meaningfully affect the lives of people with MS,” she said.
No Harm From Overheating
Commenting on the findings, Katherine Knox, MD, associate professor of physical medicine and rehabilitation at the University of Saskatchewan, Canada, noted that “the intervention maybe be initially helpful for the person fearful of getting weaker when they get ‘hot’ with exercise.”
Dr. Knox, who wasn’t involved in the research, added that it’s important for patients with MS to overcome initial barriers and fears about exercise.
“However, for most people the effects of being warm with exercise are less concerning for them after education that the weakness is temporary and does not cause harm if one takes the right precautions such as planning ahead to avoid a fall,” she said. Also, inexpensive interventions such as a fan or a wet cotton headband can be helpful, she said.
The study “provides further evidence that the ‘overheating’ is not causing harm since the time to exhaustion was unchanged,” Dr. Knox added.
The study was funded by the National Institutes of Health. The authors had no disclosures. Disclosure information for Dr. Knox was not available.
A version of this article appeared on Medscape.com.
WEST PALM BEACH, CALIFORNIA — , results from a new phase 3 trial suggested.
The findings from the randomized, placebo-controlled, double-blind study could solve this common problem, known clinically as Uhthoff’s phenomenon, that causes temporary worsening of MS symptoms with heat exposure.
“This could be a game changer,” said study investigator Victoria M. Leavitt, PhD, assistant professor of neuropsychology of Columbia University Irving Medical Center in New York City.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and published online in the Journal of Neurology.
A Common Condition
Research suggested that 60%-80% of MS patients experience heat sensitivity. However, while the exact cause is unknown, some evidence suggested it may be related to hypothalamic dysregulation or lesions of the hypothalamus.
Researchers have explored cooling strategies such as liquid-cooled clothing, but available tools can be hard to find, expensive, and cumbersome. Although aspirin has been linked to some symptom improvement in MS, its utility and that of acetaminophen for the condition has not been studied, Dr. Leavitt said.
For the single-center study, researchers recruited 60 patients (81% female; average age, 42 years; 73% White individuals) between 2019 and 2022. Overall, 37 completed at least one study visit, and 29 completed two to three visits. The average disease duration was 6 years.
Participants received oral administration of 650 mg aspirin, acetaminophen, or placebo at each of three study visits over 3 weeks, separated by at least 1 week. At each visit, they took part in a maximal exercise test conducted on a cycle ergometer and were asked to cycle at 50-60 revolutions/min for as long as possible.
Compared with placebo, body temperature increase from baseline to exercise stoppage was significantly reduced with aspirin (0.006 °F vs 0.68 °F; P < .001) and with acetaminophen (0.31 °F vs 0.68 °F; P < .004)
Neither medication was associated with a significant difference in time to exhaustion, and there were no serious adverse events.
“This is really nice because some people might have an adverse reaction to aspirin,” such as gastrointestinal issues. Acetaminophen has a different side-effect profile,” Dr. Leavitt said.
Both medications are inexpensive and available over the counter. The 650-mg acetaminophen dose used in the study is available in an extended-release formula. Typically aspirin isn’t available in doses larger than 325 mg. The 650-mg dose used in the study is considered safe but large.
Dr. Leavitt said she would like to study daily aspirin in people with MS to see if it can boost physical activity. “That’s the test of whether this will meaningfully affect the lives of people with MS,” she said.
No Harm From Overheating
Commenting on the findings, Katherine Knox, MD, associate professor of physical medicine and rehabilitation at the University of Saskatchewan, Canada, noted that “the intervention maybe be initially helpful for the person fearful of getting weaker when they get ‘hot’ with exercise.”
Dr. Knox, who wasn’t involved in the research, added that it’s important for patients with MS to overcome initial barriers and fears about exercise.
“However, for most people the effects of being warm with exercise are less concerning for them after education that the weakness is temporary and does not cause harm if one takes the right precautions such as planning ahead to avoid a fall,” she said. Also, inexpensive interventions such as a fan or a wet cotton headband can be helpful, she said.
The study “provides further evidence that the ‘overheating’ is not causing harm since the time to exhaustion was unchanged,” Dr. Knox added.
The study was funded by the National Institutes of Health. The authors had no disclosures. Disclosure information for Dr. Knox was not available.
A version of this article appeared on Medscape.com.
FROM ACTRIMS FORUM 2024
Inexperience Diagnosing Syphilis Adding to Higher Rates
With rates of syphilis rising quickly in the United States and elsewhere, clinicians are having to up their game when it comes to diagnosing and treating an infection that they may not be paying enough attention to.
More than 200,000 cases of syphilis were reported in the United States in 2022, which is the highest number since 1950 and is a 17.3% increase over 2021, according to the latest figures from the Centers for Disease Control and Prevention (CDC). The rate of infection has increased almost every year since a historic low in 2001.
And the trend is not limited to the United States. Last year, the infection rate in the United Kingdom hit a 50-year high, said David Mabey, BCh, DM, from the London School of Hygiene and Tropical Medicine. Syphilis and other sexually transmitted infections are also a major problem in low- and middle-income countries, he added, although good data are not always available.
Many of today’s healthcare professionals have little experience with the disease, shared Ina Park, MD, a sexually transmitted infections specialist at the University of California at San Francisco. “An entire generation of physicians — including myself — did not see any cases until we were well out of our training,” Dr. Park reported. “We’re really playing catch-up.”
A Centuries-Old Ailment
Dr. Park offered some advice on the challenges of diagnosing what can be an elusive infection at the Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver. That advice boiled down to one simple rule: “Test, test, test.”
Because syphilis can mimic so many other conditions and can have long periods of latency, it can be easily missed or even misdiagnosed by experienced physicians, said Dr. Park. Clinicians need to keep it front of mind and have a lower threshold for testing, even if there are no obvious symptoms.
Following the CDC’s new recommendations for syphilis screening will help, she noted; every sexually active patient aged between 15 and 44 years who lives in a county with a syphilis infection rate of 4.6 per 100,000 people or higher should get the test. And clinicians should remain vigilant, even in areas with a lower prevalence. “If you can’t account for new symptoms in a sexually active patient, order a test,” said Dr. Park.
Complicated Cases
The lack of experience with syphilis affects not just diagnosis but also treatment, particularly for complex cases, said Khalil Ghanem, MD, PhD, from the Johns Hopkins University School of Medicine in Baltimore. “When you don’t have to deal with something for a while, you forget how to deal with it,” he added.
At CROI, Dr. Ghanem offered suggestions for how to navigate complicated cases of ocular syphilis, otic syphilis, and neurosyphilis, and how to interpret test results when a patient’s antigen titers are being “unruly.”
With potential ocular or otic syphilis, you shouldn’t wait for a specialist like an ophthalmologist to weigh in but instead refer the patient directly to the emergency department because of the risk that the symptoms may become irreversible and result in permanent blindness or deafness. “You don’t want to dilly-dally with those conditions,” Dr. Ghanem said.
Closely monitoring a patient’s rapid plasma regain and venereal disease research laboratory antigen levels is the only way to manage syphilis and to determine whether the infection is responding to treatment, he noted, but sometimes those titers “don’t do what you think they should be doing” and fail to decline or even go up after treatment.
“You don’t know if they went up because the patient was re-infected, or they developed neurosyphilis, or there was a problem at the lab,” he said. “It can be challenging to interpret.”
To decipher confusing test results, Dr. Ghanem recommended getting a detailed history to understand whether a patient is at risk for reinfection, whether there are signs of neurosyphilis or other complications, whether pregnancy is possible, and so on. “Based on the answers, you can determine what the most rational approach to treatment would be,” he shared.
Drug Shortages
Efforts to get the infection under control have become more complicated. Last summer, Pfizer announced that it had run out of penicillin G benzathine (Bicillin), an injectable, long-acting drug that is one of the main treatments for syphilis and the only one that can be given to pregnant people. Supplies for children ran out at the end of June 2023, and supplies for adults were gone by the end of September.
Because Pfizer is the only company that manufactures penicillin G benzathine, there is no one to pick up the slack in the short-term, so the shortage is expected to continue until at least the middle of 2024.
In response, the US Food and Drug Administration has temporarily allowed the use of benzylpenicillin benzathine (Extencilline), a French formulation that has not been approved in the United States, until supplies of penicillin G benzathine are stabilized.
The shortage has shone a spotlight on the important issue of a lack of alternatives for the treatment of syphilis during pregnancy, which increases the risk for congenital syphilis. “Hopefully, this pushes the National Institutes of Health and others to step up their game on studies for alternative drugs for use in pregnancy,” Dr. Ghanem said.
A version of this article appeared on Medscape.com.
With rates of syphilis rising quickly in the United States and elsewhere, clinicians are having to up their game when it comes to diagnosing and treating an infection that they may not be paying enough attention to.
More than 200,000 cases of syphilis were reported in the United States in 2022, which is the highest number since 1950 and is a 17.3% increase over 2021, according to the latest figures from the Centers for Disease Control and Prevention (CDC). The rate of infection has increased almost every year since a historic low in 2001.
And the trend is not limited to the United States. Last year, the infection rate in the United Kingdom hit a 50-year high, said David Mabey, BCh, DM, from the London School of Hygiene and Tropical Medicine. Syphilis and other sexually transmitted infections are also a major problem in low- and middle-income countries, he added, although good data are not always available.
Many of today’s healthcare professionals have little experience with the disease, shared Ina Park, MD, a sexually transmitted infections specialist at the University of California at San Francisco. “An entire generation of physicians — including myself — did not see any cases until we were well out of our training,” Dr. Park reported. “We’re really playing catch-up.”
A Centuries-Old Ailment
Dr. Park offered some advice on the challenges of diagnosing what can be an elusive infection at the Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver. That advice boiled down to one simple rule: “Test, test, test.”
Because syphilis can mimic so many other conditions and can have long periods of latency, it can be easily missed or even misdiagnosed by experienced physicians, said Dr. Park. Clinicians need to keep it front of mind and have a lower threshold for testing, even if there are no obvious symptoms.
Following the CDC’s new recommendations for syphilis screening will help, she noted; every sexually active patient aged between 15 and 44 years who lives in a county with a syphilis infection rate of 4.6 per 100,000 people or higher should get the test. And clinicians should remain vigilant, even in areas with a lower prevalence. “If you can’t account for new symptoms in a sexually active patient, order a test,” said Dr. Park.
Complicated Cases
The lack of experience with syphilis affects not just diagnosis but also treatment, particularly for complex cases, said Khalil Ghanem, MD, PhD, from the Johns Hopkins University School of Medicine in Baltimore. “When you don’t have to deal with something for a while, you forget how to deal with it,” he added.
At CROI, Dr. Ghanem offered suggestions for how to navigate complicated cases of ocular syphilis, otic syphilis, and neurosyphilis, and how to interpret test results when a patient’s antigen titers are being “unruly.”
With potential ocular or otic syphilis, you shouldn’t wait for a specialist like an ophthalmologist to weigh in but instead refer the patient directly to the emergency department because of the risk that the symptoms may become irreversible and result in permanent blindness or deafness. “You don’t want to dilly-dally with those conditions,” Dr. Ghanem said.
Closely monitoring a patient’s rapid plasma regain and venereal disease research laboratory antigen levels is the only way to manage syphilis and to determine whether the infection is responding to treatment, he noted, but sometimes those titers “don’t do what you think they should be doing” and fail to decline or even go up after treatment.
“You don’t know if they went up because the patient was re-infected, or they developed neurosyphilis, or there was a problem at the lab,” he said. “It can be challenging to interpret.”
To decipher confusing test results, Dr. Ghanem recommended getting a detailed history to understand whether a patient is at risk for reinfection, whether there are signs of neurosyphilis or other complications, whether pregnancy is possible, and so on. “Based on the answers, you can determine what the most rational approach to treatment would be,” he shared.
Drug Shortages
Efforts to get the infection under control have become more complicated. Last summer, Pfizer announced that it had run out of penicillin G benzathine (Bicillin), an injectable, long-acting drug that is one of the main treatments for syphilis and the only one that can be given to pregnant people. Supplies for children ran out at the end of June 2023, and supplies for adults were gone by the end of September.
Because Pfizer is the only company that manufactures penicillin G benzathine, there is no one to pick up the slack in the short-term, so the shortage is expected to continue until at least the middle of 2024.
In response, the US Food and Drug Administration has temporarily allowed the use of benzylpenicillin benzathine (Extencilline), a French formulation that has not been approved in the United States, until supplies of penicillin G benzathine are stabilized.
The shortage has shone a spotlight on the important issue of a lack of alternatives for the treatment of syphilis during pregnancy, which increases the risk for congenital syphilis. “Hopefully, this pushes the National Institutes of Health and others to step up their game on studies for alternative drugs for use in pregnancy,” Dr. Ghanem said.
A version of this article appeared on Medscape.com.
With rates of syphilis rising quickly in the United States and elsewhere, clinicians are having to up their game when it comes to diagnosing and treating an infection that they may not be paying enough attention to.
More than 200,000 cases of syphilis were reported in the United States in 2022, which is the highest number since 1950 and is a 17.3% increase over 2021, according to the latest figures from the Centers for Disease Control and Prevention (CDC). The rate of infection has increased almost every year since a historic low in 2001.
And the trend is not limited to the United States. Last year, the infection rate in the United Kingdom hit a 50-year high, said David Mabey, BCh, DM, from the London School of Hygiene and Tropical Medicine. Syphilis and other sexually transmitted infections are also a major problem in low- and middle-income countries, he added, although good data are not always available.
Many of today’s healthcare professionals have little experience with the disease, shared Ina Park, MD, a sexually transmitted infections specialist at the University of California at San Francisco. “An entire generation of physicians — including myself — did not see any cases until we were well out of our training,” Dr. Park reported. “We’re really playing catch-up.”
A Centuries-Old Ailment
Dr. Park offered some advice on the challenges of diagnosing what can be an elusive infection at the Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver. That advice boiled down to one simple rule: “Test, test, test.”
Because syphilis can mimic so many other conditions and can have long periods of latency, it can be easily missed or even misdiagnosed by experienced physicians, said Dr. Park. Clinicians need to keep it front of mind and have a lower threshold for testing, even if there are no obvious symptoms.
Following the CDC’s new recommendations for syphilis screening will help, she noted; every sexually active patient aged between 15 and 44 years who lives in a county with a syphilis infection rate of 4.6 per 100,000 people or higher should get the test. And clinicians should remain vigilant, even in areas with a lower prevalence. “If you can’t account for new symptoms in a sexually active patient, order a test,” said Dr. Park.
Complicated Cases
The lack of experience with syphilis affects not just diagnosis but also treatment, particularly for complex cases, said Khalil Ghanem, MD, PhD, from the Johns Hopkins University School of Medicine in Baltimore. “When you don’t have to deal with something for a while, you forget how to deal with it,” he added.
At CROI, Dr. Ghanem offered suggestions for how to navigate complicated cases of ocular syphilis, otic syphilis, and neurosyphilis, and how to interpret test results when a patient’s antigen titers are being “unruly.”
With potential ocular or otic syphilis, you shouldn’t wait for a specialist like an ophthalmologist to weigh in but instead refer the patient directly to the emergency department because of the risk that the symptoms may become irreversible and result in permanent blindness or deafness. “You don’t want to dilly-dally with those conditions,” Dr. Ghanem said.
Closely monitoring a patient’s rapid plasma regain and venereal disease research laboratory antigen levels is the only way to manage syphilis and to determine whether the infection is responding to treatment, he noted, but sometimes those titers “don’t do what you think they should be doing” and fail to decline or even go up after treatment.
“You don’t know if they went up because the patient was re-infected, or they developed neurosyphilis, or there was a problem at the lab,” he said. “It can be challenging to interpret.”
To decipher confusing test results, Dr. Ghanem recommended getting a detailed history to understand whether a patient is at risk for reinfection, whether there are signs of neurosyphilis or other complications, whether pregnancy is possible, and so on. “Based on the answers, you can determine what the most rational approach to treatment would be,” he shared.
Drug Shortages
Efforts to get the infection under control have become more complicated. Last summer, Pfizer announced that it had run out of penicillin G benzathine (Bicillin), an injectable, long-acting drug that is one of the main treatments for syphilis and the only one that can be given to pregnant people. Supplies for children ran out at the end of June 2023, and supplies for adults were gone by the end of September.
Because Pfizer is the only company that manufactures penicillin G benzathine, there is no one to pick up the slack in the short-term, so the shortage is expected to continue until at least the middle of 2024.
In response, the US Food and Drug Administration has temporarily allowed the use of benzylpenicillin benzathine (Extencilline), a French formulation that has not been approved in the United States, until supplies of penicillin G benzathine are stabilized.
The shortage has shone a spotlight on the important issue of a lack of alternatives for the treatment of syphilis during pregnancy, which increases the risk for congenital syphilis. “Hopefully, this pushes the National Institutes of Health and others to step up their game on studies for alternative drugs for use in pregnancy,” Dr. Ghanem said.
A version of this article appeared on Medscape.com.
New Infant RSV Antibody Treatment Shows Strong Results
The new RSV antibody treatment for babies has been highly effective in its first season, according to a first look at data from four children’s hospitals.
Babies who received the new preventive treatment for RSV shortly after birth were 90% less likely to be severely sickened with the potentially deadly respiratory illness, according to the new estimate published by the Centers for Disease Control and Prevention. It is the first real-world evaluation of Beyfortus (the generic name is nirsevimab), which was approved by the Food and Drug Administration last July.
RSV is a seasonal illness that affects more people — particularly infants and the elderly — in the fall and winter. Symptoms are usually mild in healthy adults, but infants are particularly at risk of getting bronchiolitis, which results in exhausting wheezing and coughing in babies due to swelling in their airways and lungs. Babies who are hospitalized may need fluids and medical devices to help them breathe.
RSV peaked this season from November to January, with more than 10,000 monthly diagnoses reported to the CDC.
The new CDC analysis was conducted among about 700 babies hospitalized for severe respiratory problems from October to the end of February. Among the babies in the study, 407 were diagnosed with RSV and 292 tested negative. The researchers found that 1% of babies in the study who were diagnosed with RSV had received Beyfortus, while the remaining babies who were positive for the virus had not.
Among the babies hospitalized for other severe respiratory problems, 18% had received Beyfortus. Overall, just 59 babies among the nearly 700 in the study received Beyfortus, perhaps reflecting the short supply of the medicine the first season it was available. The report authors noted that babies in the study who did receive Beyfortus also tended to have high-risk medical conditions.
The number of babies nationwide who received Beyfortus during this first season of availability is unclear, but a January CDC survey showed that 4 in 10 parents said their babies under 8 months old had received the treatment. The Wall Street Journal reported recently that a shortage last fall resulted from underestimated demand and from production plans that were set before the CDC decided to recommend that all infants under 8 months old receive Beyfortus if their mothers did not get a maternal vaccine that can protect infants from RSV.
Both the antibody treatment for infants and the maternal vaccine were shown in clinical trials to be about 80% effective at preventing severe illness stemming from RSV.
The authors of the latest CDC report concluded that “this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.”
A version of this article appeared on WebMD.com.
The new RSV antibody treatment for babies has been highly effective in its first season, according to a first look at data from four children’s hospitals.
Babies who received the new preventive treatment for RSV shortly after birth were 90% less likely to be severely sickened with the potentially deadly respiratory illness, according to the new estimate published by the Centers for Disease Control and Prevention. It is the first real-world evaluation of Beyfortus (the generic name is nirsevimab), which was approved by the Food and Drug Administration last July.
RSV is a seasonal illness that affects more people — particularly infants and the elderly — in the fall and winter. Symptoms are usually mild in healthy adults, but infants are particularly at risk of getting bronchiolitis, which results in exhausting wheezing and coughing in babies due to swelling in their airways and lungs. Babies who are hospitalized may need fluids and medical devices to help them breathe.
RSV peaked this season from November to January, with more than 10,000 monthly diagnoses reported to the CDC.
The new CDC analysis was conducted among about 700 babies hospitalized for severe respiratory problems from October to the end of February. Among the babies in the study, 407 were diagnosed with RSV and 292 tested negative. The researchers found that 1% of babies in the study who were diagnosed with RSV had received Beyfortus, while the remaining babies who were positive for the virus had not.
Among the babies hospitalized for other severe respiratory problems, 18% had received Beyfortus. Overall, just 59 babies among the nearly 700 in the study received Beyfortus, perhaps reflecting the short supply of the medicine the first season it was available. The report authors noted that babies in the study who did receive Beyfortus also tended to have high-risk medical conditions.
The number of babies nationwide who received Beyfortus during this first season of availability is unclear, but a January CDC survey showed that 4 in 10 parents said their babies under 8 months old had received the treatment. The Wall Street Journal reported recently that a shortage last fall resulted from underestimated demand and from production plans that were set before the CDC decided to recommend that all infants under 8 months old receive Beyfortus if their mothers did not get a maternal vaccine that can protect infants from RSV.
Both the antibody treatment for infants and the maternal vaccine were shown in clinical trials to be about 80% effective at preventing severe illness stemming from RSV.
The authors of the latest CDC report concluded that “this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.”
A version of this article appeared on WebMD.com.
The new RSV antibody treatment for babies has been highly effective in its first season, according to a first look at data from four children’s hospitals.
Babies who received the new preventive treatment for RSV shortly after birth were 90% less likely to be severely sickened with the potentially deadly respiratory illness, according to the new estimate published by the Centers for Disease Control and Prevention. It is the first real-world evaluation of Beyfortus (the generic name is nirsevimab), which was approved by the Food and Drug Administration last July.
RSV is a seasonal illness that affects more people — particularly infants and the elderly — in the fall and winter. Symptoms are usually mild in healthy adults, but infants are particularly at risk of getting bronchiolitis, which results in exhausting wheezing and coughing in babies due to swelling in their airways and lungs. Babies who are hospitalized may need fluids and medical devices to help them breathe.
RSV peaked this season from November to January, with more than 10,000 monthly diagnoses reported to the CDC.
The new CDC analysis was conducted among about 700 babies hospitalized for severe respiratory problems from October to the end of February. Among the babies in the study, 407 were diagnosed with RSV and 292 tested negative. The researchers found that 1% of babies in the study who were diagnosed with RSV had received Beyfortus, while the remaining babies who were positive for the virus had not.
Among the babies hospitalized for other severe respiratory problems, 18% had received Beyfortus. Overall, just 59 babies among the nearly 700 in the study received Beyfortus, perhaps reflecting the short supply of the medicine the first season it was available. The report authors noted that babies in the study who did receive Beyfortus also tended to have high-risk medical conditions.
The number of babies nationwide who received Beyfortus during this first season of availability is unclear, but a January CDC survey showed that 4 in 10 parents said their babies under 8 months old had received the treatment. The Wall Street Journal reported recently that a shortage last fall resulted from underestimated demand and from production plans that were set before the CDC decided to recommend that all infants under 8 months old receive Beyfortus if their mothers did not get a maternal vaccine that can protect infants from RSV.
Both the antibody treatment for infants and the maternal vaccine were shown in clinical trials to be about 80% effective at preventing severe illness stemming from RSV.
The authors of the latest CDC report concluded that “this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.”
A version of this article appeared on WebMD.com.
Tirzepatide Weight Loss Consistent Regardless of BMI
Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.
The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.
The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.
More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.
Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
Weight Loss Consistent Regardless of BMI
The SURMOUNT series of trials involved people with a BMI of 30 kg/m2 and above, or 27 kg/m2 with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).
BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m2 and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.
Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.
At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.
Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.
In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.
Body Weight and Waist Circumference Reduced Regardless of Disease Duration
In this second presentation, participants were categorized based on duration with overweight/obesity at baseline (10 years or less, between 10 and 20 years, and above 20 years). Percentage body weight change; the proportions achieving weight loss targets of 5%, 10%, 15%, 20%, and 25%; and the change in waist circumference were analyzed.
Greater weight reductions were found in participants who took tirzepatide than in those who took placebo across the SURMOUNT 1-4 study endpoints, including weight reduction targets of 5%, 10%, 15%, 20%, and 25% compared with placebo-treated participants, regardless of disease duration, reported the authors in an early press release from ECO. The magnitude of weight reductions was generally similar across the disease duration categories.
For example, in the SURMOUNT-1 trial, for patients given 10-mg dose of tirzepatide, those with disease duration under 10 years lost 21% of their weight after 72 weeks compared with 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.
In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 10-mg dose of tirzepatide, those with disease duration under 10 years lost 12.6% of their body weight, while those with disease duration of 10-20 years lost 12.5%; in people living with overweight or obesity for over 20 years, 14.4% of body weight was lost.
Waist circumference also reduced to a greater extent than placebo for each disease duration category across the four studies, and again, these reductions were consistent across disease duration subgroups.
A difference between patients with and without type 2 diabetes was evident and requires further analysis to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes.
Asked to comment on the findings, Jens Juul Holst, MD, from the Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark, said that the results were as expected.
“The first abstract is said to show that there is the same effect regardless of the baseline BMI, but this is the expected outcome — nothing exciting there,” he told this news organization. “The second deals with the effects in people with different duration of adiposity. Again, it was equally effective in all groups and that was also the expected outcome, although important.”
“One question is whether one should treat people with BMI < 30 at all, and that depends on preexisting comorbidities — in particular metabolic syndrome, where treatment could be lifesaving and prevent complications,” added Dr. Holst.
This news organization also asked Jason Halford, ECO president, for his view on the findings. He remarked that with these weight loss drugs overall, “Usually weight loss tends to be proportional and actually greater in the lower BMI categories. This is partly because dosing is not done by body weight, and everyone gets the same doses irrespective of how they weigh. There is an argument that doses should be adjusted. The data suggests these drugs are so potent this does not occur for some reason.”
Dr. Holst added that, “In principle, for a given reduction in food intake, one would expect a similar reduction in body mass, and these agents should be dosed according to the size of the individual — since energy expenditure depends linearly on body weight, this is probably a reasonable measure. But what actually happens is dosing is according to the occurrence of side effects, which is a good pragmatic principle.”
Dr. Holst pointed out that the interesting question here is whether the very obese would somehow be resistant to the GLP-1 RAs (like leptin) — “they are not,” he noted.
He added that to his knowledge, the question around the role played by duration of the adiposity had not been explicitly looked at before. “However, the many individuals with obesity studied after GLP-1 RA treatment have varied widely with respect to duration and weight loss has not previously been known to depend on this, but there is no known physiological mechanism underpinning this.”
Tirzepatide (Mounjaro) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro label to include weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and at least one weight-related comorbid condition.
Dr. Holst had no conflicting interest with Eli Lilly but is a member of advisory boards for Novo Nordisk. This work (abstract 014) was funded by Eli Lilly and Company. Dr. Le Roux reported grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He served on advisory boards and speaker panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. Dr. Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. Dr. Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. Dr. Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Dr. Le Roux provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic. Dr. Aronne reported receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences, and Versanis and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. FJ, TF, MM, LG, and LN are employees and shareholders of Eli Lilly and Company.
A version of this article appeared on Medscape.com.
Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.
The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.
The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.
More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.
Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
Weight Loss Consistent Regardless of BMI
The SURMOUNT series of trials involved people with a BMI of 30 kg/m2 and above, or 27 kg/m2 with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).
BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m2 and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.
Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.
At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.
Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.
In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.
Body Weight and Waist Circumference Reduced Regardless of Disease Duration
In this second presentation, participants were categorized based on duration with overweight/obesity at baseline (10 years or less, between 10 and 20 years, and above 20 years). Percentage body weight change; the proportions achieving weight loss targets of 5%, 10%, 15%, 20%, and 25%; and the change in waist circumference were analyzed.
Greater weight reductions were found in participants who took tirzepatide than in those who took placebo across the SURMOUNT 1-4 study endpoints, including weight reduction targets of 5%, 10%, 15%, 20%, and 25% compared with placebo-treated participants, regardless of disease duration, reported the authors in an early press release from ECO. The magnitude of weight reductions was generally similar across the disease duration categories.
For example, in the SURMOUNT-1 trial, for patients given 10-mg dose of tirzepatide, those with disease duration under 10 years lost 21% of their weight after 72 weeks compared with 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.
In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 10-mg dose of tirzepatide, those with disease duration under 10 years lost 12.6% of their body weight, while those with disease duration of 10-20 years lost 12.5%; in people living with overweight or obesity for over 20 years, 14.4% of body weight was lost.
Waist circumference also reduced to a greater extent than placebo for each disease duration category across the four studies, and again, these reductions were consistent across disease duration subgroups.
A difference between patients with and without type 2 diabetes was evident and requires further analysis to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes.
Asked to comment on the findings, Jens Juul Holst, MD, from the Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark, said that the results were as expected.
“The first abstract is said to show that there is the same effect regardless of the baseline BMI, but this is the expected outcome — nothing exciting there,” he told this news organization. “The second deals with the effects in people with different duration of adiposity. Again, it was equally effective in all groups and that was also the expected outcome, although important.”
“One question is whether one should treat people with BMI < 30 at all, and that depends on preexisting comorbidities — in particular metabolic syndrome, where treatment could be lifesaving and prevent complications,” added Dr. Holst.
This news organization also asked Jason Halford, ECO president, for his view on the findings. He remarked that with these weight loss drugs overall, “Usually weight loss tends to be proportional and actually greater in the lower BMI categories. This is partly because dosing is not done by body weight, and everyone gets the same doses irrespective of how they weigh. There is an argument that doses should be adjusted. The data suggests these drugs are so potent this does not occur for some reason.”
Dr. Holst added that, “In principle, for a given reduction in food intake, one would expect a similar reduction in body mass, and these agents should be dosed according to the size of the individual — since energy expenditure depends linearly on body weight, this is probably a reasonable measure. But what actually happens is dosing is according to the occurrence of side effects, which is a good pragmatic principle.”
Dr. Holst pointed out that the interesting question here is whether the very obese would somehow be resistant to the GLP-1 RAs (like leptin) — “they are not,” he noted.
He added that to his knowledge, the question around the role played by duration of the adiposity had not been explicitly looked at before. “However, the many individuals with obesity studied after GLP-1 RA treatment have varied widely with respect to duration and weight loss has not previously been known to depend on this, but there is no known physiological mechanism underpinning this.”
Tirzepatide (Mounjaro) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro label to include weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and at least one weight-related comorbid condition.
Dr. Holst had no conflicting interest with Eli Lilly but is a member of advisory boards for Novo Nordisk. This work (abstract 014) was funded by Eli Lilly and Company. Dr. Le Roux reported grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He served on advisory boards and speaker panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. Dr. Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. Dr. Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. Dr. Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Dr. Le Roux provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic. Dr. Aronne reported receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences, and Versanis and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. FJ, TF, MM, LG, and LN are employees and shareholders of Eli Lilly and Company.
A version of this article appeared on Medscape.com.
Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.
The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.
The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.
More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.
Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
Weight Loss Consistent Regardless of BMI
The SURMOUNT series of trials involved people with a BMI of 30 kg/m2 and above, or 27 kg/m2 with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).
BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m2 and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.
Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.
At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.
Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.
In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.
Body Weight and Waist Circumference Reduced Regardless of Disease Duration
In this second presentation, participants were categorized based on duration with overweight/obesity at baseline (10 years or less, between 10 and 20 years, and above 20 years). Percentage body weight change; the proportions achieving weight loss targets of 5%, 10%, 15%, 20%, and 25%; and the change in waist circumference were analyzed.
Greater weight reductions were found in participants who took tirzepatide than in those who took placebo across the SURMOUNT 1-4 study endpoints, including weight reduction targets of 5%, 10%, 15%, 20%, and 25% compared with placebo-treated participants, regardless of disease duration, reported the authors in an early press release from ECO. The magnitude of weight reductions was generally similar across the disease duration categories.
For example, in the SURMOUNT-1 trial, for patients given 10-mg dose of tirzepatide, those with disease duration under 10 years lost 21% of their weight after 72 weeks compared with 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.
In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 10-mg dose of tirzepatide, those with disease duration under 10 years lost 12.6% of their body weight, while those with disease duration of 10-20 years lost 12.5%; in people living with overweight or obesity for over 20 years, 14.4% of body weight was lost.
Waist circumference also reduced to a greater extent than placebo for each disease duration category across the four studies, and again, these reductions were consistent across disease duration subgroups.
A difference between patients with and without type 2 diabetes was evident and requires further analysis to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes.
Asked to comment on the findings, Jens Juul Holst, MD, from the Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark, said that the results were as expected.
“The first abstract is said to show that there is the same effect regardless of the baseline BMI, but this is the expected outcome — nothing exciting there,” he told this news organization. “The second deals with the effects in people with different duration of adiposity. Again, it was equally effective in all groups and that was also the expected outcome, although important.”
“One question is whether one should treat people with BMI < 30 at all, and that depends on preexisting comorbidities — in particular metabolic syndrome, where treatment could be lifesaving and prevent complications,” added Dr. Holst.
This news organization also asked Jason Halford, ECO president, for his view on the findings. He remarked that with these weight loss drugs overall, “Usually weight loss tends to be proportional and actually greater in the lower BMI categories. This is partly because dosing is not done by body weight, and everyone gets the same doses irrespective of how they weigh. There is an argument that doses should be adjusted. The data suggests these drugs are so potent this does not occur for some reason.”
Dr. Holst added that, “In principle, for a given reduction in food intake, one would expect a similar reduction in body mass, and these agents should be dosed according to the size of the individual — since energy expenditure depends linearly on body weight, this is probably a reasonable measure. But what actually happens is dosing is according to the occurrence of side effects, which is a good pragmatic principle.”
Dr. Holst pointed out that the interesting question here is whether the very obese would somehow be resistant to the GLP-1 RAs (like leptin) — “they are not,” he noted.
He added that to his knowledge, the question around the role played by duration of the adiposity had not been explicitly looked at before. “However, the many individuals with obesity studied after GLP-1 RA treatment have varied widely with respect to duration and weight loss has not previously been known to depend on this, but there is no known physiological mechanism underpinning this.”
Tirzepatide (Mounjaro) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound) for chronic weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with at least one weight-related comorbidity. Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro label to include weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and at least one weight-related comorbid condition.
Dr. Holst had no conflicting interest with Eli Lilly but is a member of advisory boards for Novo Nordisk. This work (abstract 014) was funded by Eli Lilly and Company. Dr. Le Roux reported grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He served on advisory boards and speaker panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. Dr. Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. Dr. Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. Dr. Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. Dr. Le Roux provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic. Dr. Aronne reported receiving grants or personal fees from Altimmune, AstraZeneca, Boehringer Ingelheim, Eli Lilly, ERX, Gelesis, Intellihealth, Jamieson Wellness, Janssen, Novo Nordisk, Optum, Pfizer, Senda Biosciences, and Versanis and being a shareholder of Allurion, ERX Pharmaceuticals, Gelesis, Intellihealth, and Jamieson Wellness. FJ, TF, MM, LG, and LN are employees and shareholders of Eli Lilly and Company.
A version of this article appeared on Medscape.com.
Timing the New Meningitis Shots Serogroup Top 5’s
The first pentavalent vaccine approved against all five major serogroups of meningococcal disease has clinicians evaluating the optimal timing for vaccination, according to a new analysis.
Vaccines have helped greatly reduce the rate of invasive meningococcal disease among adolescents over the past 20 years, and the new formulation that covers all main types of the bacteria could help improve vaccination coverage and drive infection rates even lower, reported the research led by senior author Gregory Zimet from the department of pediatrics at the Indiana University School of Medicine in Indianapolis, Indiana.
The five main serogroups — labeled A, B, C, W, and Y — cause most of the disease set off by the bacteria Neisseria meningitidis. It is a rare but serious illness that mostly affects adolescents and young adults.
Meningitis often presents with nonspecific symptoms and can progress to serious illness and even death within hours.
“Clinical features of invasive meningococcal disease, coupled with its unpredictable epidemiology, suggest that vaccination is the best strategy for preventing associated adverse outcomes,” the researchers reported.
Before the introduction of vaccines in 2005, the incidence of disease in the United States ranged from 0.5 to 1.1 cases per 100,000 people, with ≥ 10% of cases being fatal.
The Quadrivalent Vaccine
In 2005, the first quadrivalent meningococcal vaccine, covering serogroups A, C, W, and Y, was approved in the United States and recommended for routine use in 11- and 12-year-olds, followed by a 2010 booster recommendation at age 16 years.
Between 2006 and 2017, the estimated incidence among 11- to 15-year-olds dropped by > 26% each year.
For those aged 16-22 years, the incidence dropped even further by > 35% per year between 2011 and 2017 after the booster was introduced.
Rates also fell in other groups that had not been vaccinated, such as in infants and adults, suggesting possible herd protection after the vaccines.
With Serogroup B
By 2015, a vaccine covering serogroup B was also approved. However, it was not added to the routine vaccination schedule and was subject to shared clinical decision-making between clinicians and patients.
The B vaccine has been less successful, reported the researchers, who said this is likely because uptake was much lower due to it not being part of the routine schedule.
Today, serogroup B makes up a greater proportion of meningitis cases. Before the vaccines were introduced, it accounted for about one third of cases, and now it is the cause of about half of all cases.
Two Doses With a Boost?
In October, the US Food and Drug Administration approved the first pentavalent vaccine against all five major serogroups, which the authors of the analysis said, “may help optimize the existing US adolescent meningococcal vaccination platform”.
A modeling study suggested that the current vaccination schedule of two doses each of the vaccines would prevent 165 cases of meningitis over 10 years. However, a two-dose pentavalent vaccine at age 11 years plus a booster at age 16 years would not only simplify the process and reduce the number of injections required but would also increase the number of cases prevented to 256.
“Use of pentavalent vaccines yields the potential to build on the success of the incumbent program, raising B vaccination coverage by simplifying existing recommendations and decreasing the number of injections required,” the researchers reported, thus “…reducing the clinical and economic burden of meningococcal disease.”
A version of this article appeared on Medscape.com.
The first pentavalent vaccine approved against all five major serogroups of meningococcal disease has clinicians evaluating the optimal timing for vaccination, according to a new analysis.
Vaccines have helped greatly reduce the rate of invasive meningococcal disease among adolescents over the past 20 years, and the new formulation that covers all main types of the bacteria could help improve vaccination coverage and drive infection rates even lower, reported the research led by senior author Gregory Zimet from the department of pediatrics at the Indiana University School of Medicine in Indianapolis, Indiana.
The five main serogroups — labeled A, B, C, W, and Y — cause most of the disease set off by the bacteria Neisseria meningitidis. It is a rare but serious illness that mostly affects adolescents and young adults.
Meningitis often presents with nonspecific symptoms and can progress to serious illness and even death within hours.
“Clinical features of invasive meningococcal disease, coupled with its unpredictable epidemiology, suggest that vaccination is the best strategy for preventing associated adverse outcomes,” the researchers reported.
Before the introduction of vaccines in 2005, the incidence of disease in the United States ranged from 0.5 to 1.1 cases per 100,000 people, with ≥ 10% of cases being fatal.
The Quadrivalent Vaccine
In 2005, the first quadrivalent meningococcal vaccine, covering serogroups A, C, W, and Y, was approved in the United States and recommended for routine use in 11- and 12-year-olds, followed by a 2010 booster recommendation at age 16 years.
Between 2006 and 2017, the estimated incidence among 11- to 15-year-olds dropped by > 26% each year.
For those aged 16-22 years, the incidence dropped even further by > 35% per year between 2011 and 2017 after the booster was introduced.
Rates also fell in other groups that had not been vaccinated, such as in infants and adults, suggesting possible herd protection after the vaccines.
With Serogroup B
By 2015, a vaccine covering serogroup B was also approved. However, it was not added to the routine vaccination schedule and was subject to shared clinical decision-making between clinicians and patients.
The B vaccine has been less successful, reported the researchers, who said this is likely because uptake was much lower due to it not being part of the routine schedule.
Today, serogroup B makes up a greater proportion of meningitis cases. Before the vaccines were introduced, it accounted for about one third of cases, and now it is the cause of about half of all cases.
Two Doses With a Boost?
In October, the US Food and Drug Administration approved the first pentavalent vaccine against all five major serogroups, which the authors of the analysis said, “may help optimize the existing US adolescent meningococcal vaccination platform”.
A modeling study suggested that the current vaccination schedule of two doses each of the vaccines would prevent 165 cases of meningitis over 10 years. However, a two-dose pentavalent vaccine at age 11 years plus a booster at age 16 years would not only simplify the process and reduce the number of injections required but would also increase the number of cases prevented to 256.
“Use of pentavalent vaccines yields the potential to build on the success of the incumbent program, raising B vaccination coverage by simplifying existing recommendations and decreasing the number of injections required,” the researchers reported, thus “…reducing the clinical and economic burden of meningococcal disease.”
A version of this article appeared on Medscape.com.
The first pentavalent vaccine approved against all five major serogroups of meningococcal disease has clinicians evaluating the optimal timing for vaccination, according to a new analysis.
Vaccines have helped greatly reduce the rate of invasive meningococcal disease among adolescents over the past 20 years, and the new formulation that covers all main types of the bacteria could help improve vaccination coverage and drive infection rates even lower, reported the research led by senior author Gregory Zimet from the department of pediatrics at the Indiana University School of Medicine in Indianapolis, Indiana.
The five main serogroups — labeled A, B, C, W, and Y — cause most of the disease set off by the bacteria Neisseria meningitidis. It is a rare but serious illness that mostly affects adolescents and young adults.
Meningitis often presents with nonspecific symptoms and can progress to serious illness and even death within hours.
“Clinical features of invasive meningococcal disease, coupled with its unpredictable epidemiology, suggest that vaccination is the best strategy for preventing associated adverse outcomes,” the researchers reported.
Before the introduction of vaccines in 2005, the incidence of disease in the United States ranged from 0.5 to 1.1 cases per 100,000 people, with ≥ 10% of cases being fatal.
The Quadrivalent Vaccine
In 2005, the first quadrivalent meningococcal vaccine, covering serogroups A, C, W, and Y, was approved in the United States and recommended for routine use in 11- and 12-year-olds, followed by a 2010 booster recommendation at age 16 years.
Between 2006 and 2017, the estimated incidence among 11- to 15-year-olds dropped by > 26% each year.
For those aged 16-22 years, the incidence dropped even further by > 35% per year between 2011 and 2017 after the booster was introduced.
Rates also fell in other groups that had not been vaccinated, such as in infants and adults, suggesting possible herd protection after the vaccines.
With Serogroup B
By 2015, a vaccine covering serogroup B was also approved. However, it was not added to the routine vaccination schedule and was subject to shared clinical decision-making between clinicians and patients.
The B vaccine has been less successful, reported the researchers, who said this is likely because uptake was much lower due to it not being part of the routine schedule.
Today, serogroup B makes up a greater proportion of meningitis cases. Before the vaccines were introduced, it accounted for about one third of cases, and now it is the cause of about half of all cases.
Two Doses With a Boost?
In October, the US Food and Drug Administration approved the first pentavalent vaccine against all five major serogroups, which the authors of the analysis said, “may help optimize the existing US adolescent meningococcal vaccination platform”.
A modeling study suggested that the current vaccination schedule of two doses each of the vaccines would prevent 165 cases of meningitis over 10 years. However, a two-dose pentavalent vaccine at age 11 years plus a booster at age 16 years would not only simplify the process and reduce the number of injections required but would also increase the number of cases prevented to 256.
“Use of pentavalent vaccines yields the potential to build on the success of the incumbent program, raising B vaccination coverage by simplifying existing recommendations and decreasing the number of injections required,” the researchers reported, thus “…reducing the clinical and economic burden of meningococcal disease.”
A version of this article appeared on Medscape.com.
Multimodal Treatment Found Effective for Overactive Bladder
TOPLINE:
A new study published in JAMA Network Open showed that an intervention including cognitive behavioral therapy improved the quality of life for women with overactive bladder (OAB).
METHODOLOGY:
- A total of 79 women with moderate to severe OAB were randomized to the control group or the intervention, which was composed of four 30-minute sessions using strategies including cognitive behavioral therapy (CBT).
- The first and second sessions provided education on OAB and CBT, lifestyle modifications such as limiting coffee intake, pelvic floor muscle training, and introduced exposure training.
- The third and fourth sessions continued exposure and pelvic floor muscle training and education on relapse prevention.
- Researchers assessed outcomes using the health-related quality of life (HRQOL), in which participants answered questions regarding their degree of distress, emotions, and physical and social limitations related to OAB symptoms.
TAKEAWAY:
- Participants who received the intervention on average improved in their HRQOL score by 12.6 points higher than those in the control group (usual care) from baseline to week 13 (between-group difference estimate, 12.6 [95% CI, 6.6-18.6] points; P < .001).
- The average age of participants was 63.5 years, and more than 87% of women in each group had moderate OAB.
- Patient-reported improvement and satisfaction scores were also more improved in the intervention group than in the control group; most participants in both groups had no change in the pharmacotherapy during the trial.
IN PRACTICE:
Urologists and other primary care clinicians who treat women with OAB may consider a multicomponent intervention that includes cognitive components and exposure-based bladder training or could refer to a cognitive behavioral therapist or pelvic floor physical therapist experienced in these techniques.
SOURCE:
Satoshi Funada, MD, PhD, and Takashi Kobayashi, MD, PhD, both with the Department of Urology at Kyoto University Graduate School of Medicine in Kyoto, Japan, are the corresponding authors. The study was published online in JAMA Network Open.
LIMITATIONS:
The trial was open label, and the use of a waiting list control group is known to produce greater differences between the two groups. The trial included patients both taking and not taking medication for OAB. The sample size was also relatively small, and the intervention was performed by a single clinician, possibly limiting the generalizability of results.
DISCLOSURES:
The study was funded by the Japan Society for the Promotion of Science (JSPS). Various study authors reported receiving grants from the Pfizer Health Research Foundation, AstraZeneca, and JSPS. Other study authors reported receiving personal fees from Eisai, Sawai Pharmaceutical, Statcom, and others. One author reported pending patents for intellectual properties for the Kokoro app licensed to Mitsubishi Tanabe Pharma.
A version of this article appeared on Medscape.com.
TOPLINE:
A new study published in JAMA Network Open showed that an intervention including cognitive behavioral therapy improved the quality of life for women with overactive bladder (OAB).
METHODOLOGY:
- A total of 79 women with moderate to severe OAB were randomized to the control group or the intervention, which was composed of four 30-minute sessions using strategies including cognitive behavioral therapy (CBT).
- The first and second sessions provided education on OAB and CBT, lifestyle modifications such as limiting coffee intake, pelvic floor muscle training, and introduced exposure training.
- The third and fourth sessions continued exposure and pelvic floor muscle training and education on relapse prevention.
- Researchers assessed outcomes using the health-related quality of life (HRQOL), in which participants answered questions regarding their degree of distress, emotions, and physical and social limitations related to OAB symptoms.
TAKEAWAY:
- Participants who received the intervention on average improved in their HRQOL score by 12.6 points higher than those in the control group (usual care) from baseline to week 13 (between-group difference estimate, 12.6 [95% CI, 6.6-18.6] points; P < .001).
- The average age of participants was 63.5 years, and more than 87% of women in each group had moderate OAB.
- Patient-reported improvement and satisfaction scores were also more improved in the intervention group than in the control group; most participants in both groups had no change in the pharmacotherapy during the trial.
IN PRACTICE:
Urologists and other primary care clinicians who treat women with OAB may consider a multicomponent intervention that includes cognitive components and exposure-based bladder training or could refer to a cognitive behavioral therapist or pelvic floor physical therapist experienced in these techniques.
SOURCE:
Satoshi Funada, MD, PhD, and Takashi Kobayashi, MD, PhD, both with the Department of Urology at Kyoto University Graduate School of Medicine in Kyoto, Japan, are the corresponding authors. The study was published online in JAMA Network Open.
LIMITATIONS:
The trial was open label, and the use of a waiting list control group is known to produce greater differences between the two groups. The trial included patients both taking and not taking medication for OAB. The sample size was also relatively small, and the intervention was performed by a single clinician, possibly limiting the generalizability of results.
DISCLOSURES:
The study was funded by the Japan Society for the Promotion of Science (JSPS). Various study authors reported receiving grants from the Pfizer Health Research Foundation, AstraZeneca, and JSPS. Other study authors reported receiving personal fees from Eisai, Sawai Pharmaceutical, Statcom, and others. One author reported pending patents for intellectual properties for the Kokoro app licensed to Mitsubishi Tanabe Pharma.
A version of this article appeared on Medscape.com.
TOPLINE:
A new study published in JAMA Network Open showed that an intervention including cognitive behavioral therapy improved the quality of life for women with overactive bladder (OAB).
METHODOLOGY:
- A total of 79 women with moderate to severe OAB were randomized to the control group or the intervention, which was composed of four 30-minute sessions using strategies including cognitive behavioral therapy (CBT).
- The first and second sessions provided education on OAB and CBT, lifestyle modifications such as limiting coffee intake, pelvic floor muscle training, and introduced exposure training.
- The third and fourth sessions continued exposure and pelvic floor muscle training and education on relapse prevention.
- Researchers assessed outcomes using the health-related quality of life (HRQOL), in which participants answered questions regarding their degree of distress, emotions, and physical and social limitations related to OAB symptoms.
TAKEAWAY:
- Participants who received the intervention on average improved in their HRQOL score by 12.6 points higher than those in the control group (usual care) from baseline to week 13 (between-group difference estimate, 12.6 [95% CI, 6.6-18.6] points; P < .001).
- The average age of participants was 63.5 years, and more than 87% of women in each group had moderate OAB.
- Patient-reported improvement and satisfaction scores were also more improved in the intervention group than in the control group; most participants in both groups had no change in the pharmacotherapy during the trial.
IN PRACTICE:
Urologists and other primary care clinicians who treat women with OAB may consider a multicomponent intervention that includes cognitive components and exposure-based bladder training or could refer to a cognitive behavioral therapist or pelvic floor physical therapist experienced in these techniques.
SOURCE:
Satoshi Funada, MD, PhD, and Takashi Kobayashi, MD, PhD, both with the Department of Urology at Kyoto University Graduate School of Medicine in Kyoto, Japan, are the corresponding authors. The study was published online in JAMA Network Open.
LIMITATIONS:
The trial was open label, and the use of a waiting list control group is known to produce greater differences between the two groups. The trial included patients both taking and not taking medication for OAB. The sample size was also relatively small, and the intervention was performed by a single clinician, possibly limiting the generalizability of results.
DISCLOSURES:
The study was funded by the Japan Society for the Promotion of Science (JSPS). Various study authors reported receiving grants from the Pfizer Health Research Foundation, AstraZeneca, and JSPS. Other study authors reported receiving personal fees from Eisai, Sawai Pharmaceutical, Statcom, and others. One author reported pending patents for intellectual properties for the Kokoro app licensed to Mitsubishi Tanabe Pharma.
A version of this article appeared on Medscape.com.
Sudden onset of symptoms
Migraines are episodic or chronic headaches, typically occurring on one side of the head, that have distinct characteristics and definitions from the International Classification of Headache Disorders, 3rd edition (ICHD 3). Migraine can occur at any age and is thought to affect about 5% of children before puberty, increases in prevalence after puberty, and reaches about 30% prevalence at age 25-30 years. Patients with migraine with aura have recurrent, fully reversible symptoms that can include diplopia, motor or sensory disturbances, and/or trouble with language that generally precede headache development. In some cases, aura may develop and resolve without headache. Migraine with aura can present at any age from early childhood onward and is present in about 30% of children and adolescents with migraine. In general, migraine with aura is more prevalent in female than in male individuals, especially adolescents.
Migraine with brainstem aura, as is the case here, is a specific subtype of migraine with aura, in which the aura specifically reflects an origin within the brainstem. Brainstem symptoms include diplopia, vertigo, difficulty controlling speech muscles, tinnitus, hearing loss, loss of coordination, and possibly impaired consciousness. For the diagnosis of migraine with brainstem aura, patients must not have motor or retinal symptoms. Aura development often is preceded by premonitory symptoms, such as fatigue, hunger or food cravings, and mood elevations.
Migraine without aura, in contrast, is characterized by recurrent moderate to severe pulsating headache lasting from a few hours to up to 3 days. Migraine without aura often causes nausea and sensitivity to light and/or sound.
Chronic migraine is defined as headache (with or without aura) occurring 15 or more days per month for at least the past 3 months. This patient's history does not fit the definition of chronic migraine.
Tension-type headaches generally are bilateral, with durations ranging from minutes to days. They tend to be mild to moderate in intensity and symptoms are not worsened by physical activity. In addition to their bilateral nature, these headaches differ from migraine in lacking associated visual, cortical, or other symptoms.
Any diagnosis of migraine requires assessment over time, using diagnostic criteria established by the International Headache Society in ICHD 3. It is not necessary to perform neuroimaging studies or CT in patients with migraine symptoms and an otherwise normal neurologic exam.
When a diagnosis of migraine with brainstem aura is established, pediatric or adolescent patients and their families should first be counseled on nonpharmacologic interventions. These interventions, which have demonstrated benefits in reducing headache frequency, include lifestyle modifications, regular sleep and meal schedules, adequate fluid intake, cognitive-behavioral therapy, stress management techniques, massage, and biofeedback techniques. Recommended for acute treatment of migraine are nonsteroidal anti-inflammatory drugs, acetaminophen, and triptans. There is limited evidence in pediatric or adolescent patients with use of preventive medications, such as topiramate, amitriptyline, or onabotulinumtoxinA. In clinical trials, patients receiving placebo saw improvements, and active treatments were only marginally, if at all, more effective. Current guidelines recommend a frank discussion with parents about the limitations of preventive therapies before making decisions to use them.
Heidi Moawad, MD, Clinical Assistant Professor, Department of Medical Education, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Heidi Moawad, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
Migraines are episodic or chronic headaches, typically occurring on one side of the head, that have distinct characteristics and definitions from the International Classification of Headache Disorders, 3rd edition (ICHD 3). Migraine can occur at any age and is thought to affect about 5% of children before puberty, increases in prevalence after puberty, and reaches about 30% prevalence at age 25-30 years. Patients with migraine with aura have recurrent, fully reversible symptoms that can include diplopia, motor or sensory disturbances, and/or trouble with language that generally precede headache development. In some cases, aura may develop and resolve without headache. Migraine with aura can present at any age from early childhood onward and is present in about 30% of children and adolescents with migraine. In general, migraine with aura is more prevalent in female than in male individuals, especially adolescents.
Migraine with brainstem aura, as is the case here, is a specific subtype of migraine with aura, in which the aura specifically reflects an origin within the brainstem. Brainstem symptoms include diplopia, vertigo, difficulty controlling speech muscles, tinnitus, hearing loss, loss of coordination, and possibly impaired consciousness. For the diagnosis of migraine with brainstem aura, patients must not have motor or retinal symptoms. Aura development often is preceded by premonitory symptoms, such as fatigue, hunger or food cravings, and mood elevations.
Migraine without aura, in contrast, is characterized by recurrent moderate to severe pulsating headache lasting from a few hours to up to 3 days. Migraine without aura often causes nausea and sensitivity to light and/or sound.
Chronic migraine is defined as headache (with or without aura) occurring 15 or more days per month for at least the past 3 months. This patient's history does not fit the definition of chronic migraine.
Tension-type headaches generally are bilateral, with durations ranging from minutes to days. They tend to be mild to moderate in intensity and symptoms are not worsened by physical activity. In addition to their bilateral nature, these headaches differ from migraine in lacking associated visual, cortical, or other symptoms.
Any diagnosis of migraine requires assessment over time, using diagnostic criteria established by the International Headache Society in ICHD 3. It is not necessary to perform neuroimaging studies or CT in patients with migraine symptoms and an otherwise normal neurologic exam.
When a diagnosis of migraine with brainstem aura is established, pediatric or adolescent patients and their families should first be counseled on nonpharmacologic interventions. These interventions, which have demonstrated benefits in reducing headache frequency, include lifestyle modifications, regular sleep and meal schedules, adequate fluid intake, cognitive-behavioral therapy, stress management techniques, massage, and biofeedback techniques. Recommended for acute treatment of migraine are nonsteroidal anti-inflammatory drugs, acetaminophen, and triptans. There is limited evidence in pediatric or adolescent patients with use of preventive medications, such as topiramate, amitriptyline, or onabotulinumtoxinA. In clinical trials, patients receiving placebo saw improvements, and active treatments were only marginally, if at all, more effective. Current guidelines recommend a frank discussion with parents about the limitations of preventive therapies before making decisions to use them.
Heidi Moawad, MD, Clinical Assistant Professor, Department of Medical Education, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Heidi Moawad, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
Migraines are episodic or chronic headaches, typically occurring on one side of the head, that have distinct characteristics and definitions from the International Classification of Headache Disorders, 3rd edition (ICHD 3). Migraine can occur at any age and is thought to affect about 5% of children before puberty, increases in prevalence after puberty, and reaches about 30% prevalence at age 25-30 years. Patients with migraine with aura have recurrent, fully reversible symptoms that can include diplopia, motor or sensory disturbances, and/or trouble with language that generally precede headache development. In some cases, aura may develop and resolve without headache. Migraine with aura can present at any age from early childhood onward and is present in about 30% of children and adolescents with migraine. In general, migraine with aura is more prevalent in female than in male individuals, especially adolescents.
Migraine with brainstem aura, as is the case here, is a specific subtype of migraine with aura, in which the aura specifically reflects an origin within the brainstem. Brainstem symptoms include diplopia, vertigo, difficulty controlling speech muscles, tinnitus, hearing loss, loss of coordination, and possibly impaired consciousness. For the diagnosis of migraine with brainstem aura, patients must not have motor or retinal symptoms. Aura development often is preceded by premonitory symptoms, such as fatigue, hunger or food cravings, and mood elevations.
Migraine without aura, in contrast, is characterized by recurrent moderate to severe pulsating headache lasting from a few hours to up to 3 days. Migraine without aura often causes nausea and sensitivity to light and/or sound.
Chronic migraine is defined as headache (with or without aura) occurring 15 or more days per month for at least the past 3 months. This patient's history does not fit the definition of chronic migraine.
Tension-type headaches generally are bilateral, with durations ranging from minutes to days. They tend to be mild to moderate in intensity and symptoms are not worsened by physical activity. In addition to their bilateral nature, these headaches differ from migraine in lacking associated visual, cortical, or other symptoms.
Any diagnosis of migraine requires assessment over time, using diagnostic criteria established by the International Headache Society in ICHD 3. It is not necessary to perform neuroimaging studies or CT in patients with migraine symptoms and an otherwise normal neurologic exam.
When a diagnosis of migraine with brainstem aura is established, pediatric or adolescent patients and their families should first be counseled on nonpharmacologic interventions. These interventions, which have demonstrated benefits in reducing headache frequency, include lifestyle modifications, regular sleep and meal schedules, adequate fluid intake, cognitive-behavioral therapy, stress management techniques, massage, and biofeedback techniques. Recommended for acute treatment of migraine are nonsteroidal anti-inflammatory drugs, acetaminophen, and triptans. There is limited evidence in pediatric or adolescent patients with use of preventive medications, such as topiramate, amitriptyline, or onabotulinumtoxinA. In clinical trials, patients receiving placebo saw improvements, and active treatments were only marginally, if at all, more effective. Current guidelines recommend a frank discussion with parents about the limitations of preventive therapies before making decisions to use them.
Heidi Moawad, MD, Clinical Assistant Professor, Department of Medical Education, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Heidi Moawad, MD, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 13-year-old girl presents with symptoms of sudden onset of double vision, vertigo, and ataxia that have occurred six or seven times over the past 2 months and usually precede a headache. These symptoms generally last less than 10 minutes. The girl says she has noticed that she often feels a bit manic and has food cravings a few hours before the double vision and other symptoms occur. She is an athlete at school but says during these attacks she avoids even walking around the house because the movement makes her symptoms worse. She has no muscle weakness or changes on her ophthalmologic exam.
No obvious issues on physical exam nor evidence of visual or neurologic deficits are present at the time of the office visit; the patient has 20/20 vision. Relevant medical history includes menarche at age 12 years. The patient is on the track team at school and is physically fit, without previous evidence of balance or other neurologic issues.
Adolescent Risk and Resilience
Bullying, heavy social media use, experimentation with drugs and alcohol: These are the well-described hazards of adolescence. We have growing knowledge of the risks associated with these experiences and which youth are more vulnerable to these risks. Developmentally, adolescence is a time of critical brain development marked by heightened sensitivity to social approval and limited impulse control. Adolescents also have growing autonomy from parents alongside a stronger need for time with friends (the new peer home away from the parental home). These factors alone make adolescence a period of heightened sensitivity to these experiences, but some youth have greater vulnerability to develop psychopathology such as anxiety, depression, eating disorders, or addiction after exposure to these common experiences. Pediatricians can assess these broader vulnerabilities during well child visits of pre- and early teens and offer patients and their parents strategies for minimizing risk and cultivating resilience.
Bullying
Bullying, both verbal and physical, has long been an unwelcome part of youth. Cellphones and social media have brought bullying into the 21st century. Cyberbullying has meant that targeted youth are no longer safe after school and it carries higher risk of self-harm and suicidality than the analog version. No child benefits from bullying, but some children are more vulnerable to develop an anxiety or mood disorder, self-injury, or suicidality, whereas others experience stress and distress, but are able to adaptively seek support from friends and adults and stay on track developmentally, even to flourish. There is evidence that girls and LGBTQ youth are more commonly bullied and at higher risk for depression, self-harm, and suicidality as a consequence of cyberbullying. Youth already suffering from a psychiatric illness or substance abuse who are bullied are at higher risk for self-harm and suicidality than that of their bullied peers. Youth whose parents score high on measures of distress and family dysfunction also face higher risk of self-harm and suicidality after bullying.1
Social Media
Unlike bullying, social media has been a force only in 21st century life, with Facebook starting in 2004 and cellphones in common use by adolescents in the past 2 decades. While there are potential benefits of social media use, such as stronger connections to supportive peers for isolated LGBTQ youth or youth who live in rural areas, there are also risks. Of course, social media carries the risk of cyberbullying. It also carries the risk for very heavy patterns of use that can interfere with physical activity, adequate sleep, academic performance, and healthy in-person social activities. There is robust emerging evidence that heavy users have higher rates of mood disorders and anxiety symptoms, although it is unclear whether social media exacerbates, or more social media use is the result of depression and/or anxiety. Adolescents’ desire for social acceptance makes them especially sensitive to the social rewards of “likes” and they are thus vulnerable to becoming heavy users. Adolescent girls who are heavy users are vulnerable to developing a disordered body image and eating disorders. Those youth with especially low levels of impulse control, such as those with ADHD, have greater risk of developing problematic use.2-4
Substance Use and Abuse
Exploration of alcohol and drug use has been a common experience, and hazard, of adolescence for many generations. As a result, we have richer knowledge of those factors that are associated with risk of and protection against that use progressing to a use disorder. Earlier age at first experimentation appears to be independently correlated with increased risk of developing a substance use disorder. Every pediatrician should be aware of a family history of substance use disorders, especially alcohol, as they are strongly associated with higher risk. Youth with temperaments that are sensation seeking, externalizing and impulsive are at higher risk. Youth with anxiety and mood disorders and untreated attention deficit disorders are at higher risk. Youth whose parents have high levels of conflict or “permissive” parenting styles are at higher risk as are those who as children experienced abuse or neglect.5-7
Minimizing Risk and Cultivating Resilience
Protective factors balance these risks: adequate sleep; positive relationships with friends and parents; and confidence in their academic, athletic, or social abilities all are correlated with good outcomes after bullying, drug and alcohol use, and social media use. These teenagers are meaningfully connected to caring adults and peers, have a future orientation, and typically have higher self-esteem. Youth whose parents balance attunement with rules and expectations (“authoritative” parenting) appear to be at lower risk of poor mental health outcomes associated with heavy social media use as well as other risk behaviors. These parents have clear rules and expectations, including about drugs and alcohol, and enforce rules reasonably calmly and consistently. Youth whose families eat dinner together at least three times weekly, who attend schools that offer a wide range of after-school activities, and who learn to use problem-focused coping skills rather than emotion-focused coping skills are protected against poor mental health outcomes in the face of these challenges.
While bullying is a stressor, social media and substances may seem like ways of managing stress and connecting with peers. There are youth with clear vulnerabilities to the risks associated with each of them. Shared factors include vulnerable temperaments, high conflict or permissive parenting, family history of substance use disorders or preexisting psychiatric illness. Pediatricians are in a unique position to raise teenagers’ awareness of their specific vulnerabilities. Talk about the heightened risk of experimentation with alcohol or drugs in your patients who are in treatment for an anxiety or mood disorder. Help them cultivate critical thinking — an adolescent specialty — around marketing and peer pressure. Remind them that social media companies make money from keeping them online longer. Then help them identify what strategies are in their control, such as limiting their time online. What else could they be doing with their time that they actually enjoy? Remind them about the value of protecting time for adequate sleep, regular exercise, and sitting down for dinner with their family. Ask about their nourishing relationships with peers and adults and talk about the value of protecting time for them. Ask your patients and their parents about how they face stress, emphasizing their ability to locate what is within their control. While awareness of feelings is important, learning to manage intense emotions is more connected to healthy habits of sleep and exercise and strategies to get support or pivot to engaging activities. Discussing this openly models for parents how to bear difficulty alongside their children without becoming distressed or punitive themselves. Talk with worried parents about the value of regular meals together, shared physical activities, and supporting time for their children’s emerging interests and hobbies. Equipping your patients and their parents with knowledge about their particular vulnerabilities, reminders about what is known about these risks, and all that is in their power to build resilience, may be as meaningful a public health intervention as asking them about biking with helmets and using seat belts.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.
References
1. Zych I et al. Protective Factors Against Bullying and Cyberbullying: A Systematic Review of Meta-Analyses. Aggress Violent Behav. 2019;45:4-19. doi: 10.1016/j.avb.2018.06.008.
2. Office of the Surgeon General. Social Media and Youth Mental Health: The U.S. Surgeon General’s Advisory. 2023. https://www.ncbi.nlm.nih.gov/books/NBK594761/.
3. Uhls Y et al. Benefits and Costs of Social Media in Adolescence. Pediatrics. 2017 Nov;140(Suppl 2):S67-S70. doi: 10.1542/peds.2016-1758E.
4. Health Advisory on Social Media Use in Adolescence. American Psychological Association (2023).
5. Sloboda Z et al. Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention, Substance Use and Misuse, Subst Use Misuse. 2012 Jun-Jul;47(8-9):944-62. doi: 10.3109/10826084.2012.663280.
6. O’Connell M et al. Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press and US Department of Health and Human Services, Substance Abuse and Mental Health Administration. 2009 (https://nap.nationalacademies.org/catalog/12480/preventing-mental-emotional-and-behavioral-disorders-among-young-people-progress).
7. Staiger P et al. Can Emotion-Focused Coping Help Explain the Link Between Posttraumatic Stress Disorder Severity and Triggers for Substance Use in Young Adults? J Subst Abuse Treat. 2009 Mar;36(2):220-6. doi: 10.1016/j.jsat.2008.05.008.
Bullying, heavy social media use, experimentation with drugs and alcohol: These are the well-described hazards of adolescence. We have growing knowledge of the risks associated with these experiences and which youth are more vulnerable to these risks. Developmentally, adolescence is a time of critical brain development marked by heightened sensitivity to social approval and limited impulse control. Adolescents also have growing autonomy from parents alongside a stronger need for time with friends (the new peer home away from the parental home). These factors alone make adolescence a period of heightened sensitivity to these experiences, but some youth have greater vulnerability to develop psychopathology such as anxiety, depression, eating disorders, or addiction after exposure to these common experiences. Pediatricians can assess these broader vulnerabilities during well child visits of pre- and early teens and offer patients and their parents strategies for minimizing risk and cultivating resilience.
Bullying
Bullying, both verbal and physical, has long been an unwelcome part of youth. Cellphones and social media have brought bullying into the 21st century. Cyberbullying has meant that targeted youth are no longer safe after school and it carries higher risk of self-harm and suicidality than the analog version. No child benefits from bullying, but some children are more vulnerable to develop an anxiety or mood disorder, self-injury, or suicidality, whereas others experience stress and distress, but are able to adaptively seek support from friends and adults and stay on track developmentally, even to flourish. There is evidence that girls and LGBTQ youth are more commonly bullied and at higher risk for depression, self-harm, and suicidality as a consequence of cyberbullying. Youth already suffering from a psychiatric illness or substance abuse who are bullied are at higher risk for self-harm and suicidality than that of their bullied peers. Youth whose parents score high on measures of distress and family dysfunction also face higher risk of self-harm and suicidality after bullying.1
Social Media
Unlike bullying, social media has been a force only in 21st century life, with Facebook starting in 2004 and cellphones in common use by adolescents in the past 2 decades. While there are potential benefits of social media use, such as stronger connections to supportive peers for isolated LGBTQ youth or youth who live in rural areas, there are also risks. Of course, social media carries the risk of cyberbullying. It also carries the risk for very heavy patterns of use that can interfere with physical activity, adequate sleep, academic performance, and healthy in-person social activities. There is robust emerging evidence that heavy users have higher rates of mood disorders and anxiety symptoms, although it is unclear whether social media exacerbates, or more social media use is the result of depression and/or anxiety. Adolescents’ desire for social acceptance makes them especially sensitive to the social rewards of “likes” and they are thus vulnerable to becoming heavy users. Adolescent girls who are heavy users are vulnerable to developing a disordered body image and eating disorders. Those youth with especially low levels of impulse control, such as those with ADHD, have greater risk of developing problematic use.2-4
Substance Use and Abuse
Exploration of alcohol and drug use has been a common experience, and hazard, of adolescence for many generations. As a result, we have richer knowledge of those factors that are associated with risk of and protection against that use progressing to a use disorder. Earlier age at first experimentation appears to be independently correlated with increased risk of developing a substance use disorder. Every pediatrician should be aware of a family history of substance use disorders, especially alcohol, as they are strongly associated with higher risk. Youth with temperaments that are sensation seeking, externalizing and impulsive are at higher risk. Youth with anxiety and mood disorders and untreated attention deficit disorders are at higher risk. Youth whose parents have high levels of conflict or “permissive” parenting styles are at higher risk as are those who as children experienced abuse or neglect.5-7
Minimizing Risk and Cultivating Resilience
Protective factors balance these risks: adequate sleep; positive relationships with friends and parents; and confidence in their academic, athletic, or social abilities all are correlated with good outcomes after bullying, drug and alcohol use, and social media use. These teenagers are meaningfully connected to caring adults and peers, have a future orientation, and typically have higher self-esteem. Youth whose parents balance attunement with rules and expectations (“authoritative” parenting) appear to be at lower risk of poor mental health outcomes associated with heavy social media use as well as other risk behaviors. These parents have clear rules and expectations, including about drugs and alcohol, and enforce rules reasonably calmly and consistently. Youth whose families eat dinner together at least three times weekly, who attend schools that offer a wide range of after-school activities, and who learn to use problem-focused coping skills rather than emotion-focused coping skills are protected against poor mental health outcomes in the face of these challenges.
While bullying is a stressor, social media and substances may seem like ways of managing stress and connecting with peers. There are youth with clear vulnerabilities to the risks associated with each of them. Shared factors include vulnerable temperaments, high conflict or permissive parenting, family history of substance use disorders or preexisting psychiatric illness. Pediatricians are in a unique position to raise teenagers’ awareness of their specific vulnerabilities. Talk about the heightened risk of experimentation with alcohol or drugs in your patients who are in treatment for an anxiety or mood disorder. Help them cultivate critical thinking — an adolescent specialty — around marketing and peer pressure. Remind them that social media companies make money from keeping them online longer. Then help them identify what strategies are in their control, such as limiting their time online. What else could they be doing with their time that they actually enjoy? Remind them about the value of protecting time for adequate sleep, regular exercise, and sitting down for dinner with their family. Ask about their nourishing relationships with peers and adults and talk about the value of protecting time for them. Ask your patients and their parents about how they face stress, emphasizing their ability to locate what is within their control. While awareness of feelings is important, learning to manage intense emotions is more connected to healthy habits of sleep and exercise and strategies to get support or pivot to engaging activities. Discussing this openly models for parents how to bear difficulty alongside their children without becoming distressed or punitive themselves. Talk with worried parents about the value of regular meals together, shared physical activities, and supporting time for their children’s emerging interests and hobbies. Equipping your patients and their parents with knowledge about their particular vulnerabilities, reminders about what is known about these risks, and all that is in their power to build resilience, may be as meaningful a public health intervention as asking them about biking with helmets and using seat belts.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.
References
1. Zych I et al. Protective Factors Against Bullying and Cyberbullying: A Systematic Review of Meta-Analyses. Aggress Violent Behav. 2019;45:4-19. doi: 10.1016/j.avb.2018.06.008.
2. Office of the Surgeon General. Social Media and Youth Mental Health: The U.S. Surgeon General’s Advisory. 2023. https://www.ncbi.nlm.nih.gov/books/NBK594761/.
3. Uhls Y et al. Benefits and Costs of Social Media in Adolescence. Pediatrics. 2017 Nov;140(Suppl 2):S67-S70. doi: 10.1542/peds.2016-1758E.
4. Health Advisory on Social Media Use in Adolescence. American Psychological Association (2023).
5. Sloboda Z et al. Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention, Substance Use and Misuse, Subst Use Misuse. 2012 Jun-Jul;47(8-9):944-62. doi: 10.3109/10826084.2012.663280.
6. O’Connell M et al. Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press and US Department of Health and Human Services, Substance Abuse and Mental Health Administration. 2009 (https://nap.nationalacademies.org/catalog/12480/preventing-mental-emotional-and-behavioral-disorders-among-young-people-progress).
7. Staiger P et al. Can Emotion-Focused Coping Help Explain the Link Between Posttraumatic Stress Disorder Severity and Triggers for Substance Use in Young Adults? J Subst Abuse Treat. 2009 Mar;36(2):220-6. doi: 10.1016/j.jsat.2008.05.008.
Bullying, heavy social media use, experimentation with drugs and alcohol: These are the well-described hazards of adolescence. We have growing knowledge of the risks associated with these experiences and which youth are more vulnerable to these risks. Developmentally, adolescence is a time of critical brain development marked by heightened sensitivity to social approval and limited impulse control. Adolescents also have growing autonomy from parents alongside a stronger need for time with friends (the new peer home away from the parental home). These factors alone make adolescence a period of heightened sensitivity to these experiences, but some youth have greater vulnerability to develop psychopathology such as anxiety, depression, eating disorders, or addiction after exposure to these common experiences. Pediatricians can assess these broader vulnerabilities during well child visits of pre- and early teens and offer patients and their parents strategies for minimizing risk and cultivating resilience.
Bullying
Bullying, both verbal and physical, has long been an unwelcome part of youth. Cellphones and social media have brought bullying into the 21st century. Cyberbullying has meant that targeted youth are no longer safe after school and it carries higher risk of self-harm and suicidality than the analog version. No child benefits from bullying, but some children are more vulnerable to develop an anxiety or mood disorder, self-injury, or suicidality, whereas others experience stress and distress, but are able to adaptively seek support from friends and adults and stay on track developmentally, even to flourish. There is evidence that girls and LGBTQ youth are more commonly bullied and at higher risk for depression, self-harm, and suicidality as a consequence of cyberbullying. Youth already suffering from a psychiatric illness or substance abuse who are bullied are at higher risk for self-harm and suicidality than that of their bullied peers. Youth whose parents score high on measures of distress and family dysfunction also face higher risk of self-harm and suicidality after bullying.1
Social Media
Unlike bullying, social media has been a force only in 21st century life, with Facebook starting in 2004 and cellphones in common use by adolescents in the past 2 decades. While there are potential benefits of social media use, such as stronger connections to supportive peers for isolated LGBTQ youth or youth who live in rural areas, there are also risks. Of course, social media carries the risk of cyberbullying. It also carries the risk for very heavy patterns of use that can interfere with physical activity, adequate sleep, academic performance, and healthy in-person social activities. There is robust emerging evidence that heavy users have higher rates of mood disorders and anxiety symptoms, although it is unclear whether social media exacerbates, or more social media use is the result of depression and/or anxiety. Adolescents’ desire for social acceptance makes them especially sensitive to the social rewards of “likes” and they are thus vulnerable to becoming heavy users. Adolescent girls who are heavy users are vulnerable to developing a disordered body image and eating disorders. Those youth with especially low levels of impulse control, such as those with ADHD, have greater risk of developing problematic use.2-4
Substance Use and Abuse
Exploration of alcohol and drug use has been a common experience, and hazard, of adolescence for many generations. As a result, we have richer knowledge of those factors that are associated with risk of and protection against that use progressing to a use disorder. Earlier age at first experimentation appears to be independently correlated with increased risk of developing a substance use disorder. Every pediatrician should be aware of a family history of substance use disorders, especially alcohol, as they are strongly associated with higher risk. Youth with temperaments that are sensation seeking, externalizing and impulsive are at higher risk. Youth with anxiety and mood disorders and untreated attention deficit disorders are at higher risk. Youth whose parents have high levels of conflict or “permissive” parenting styles are at higher risk as are those who as children experienced abuse or neglect.5-7
Minimizing Risk and Cultivating Resilience
Protective factors balance these risks: adequate sleep; positive relationships with friends and parents; and confidence in their academic, athletic, or social abilities all are correlated with good outcomes after bullying, drug and alcohol use, and social media use. These teenagers are meaningfully connected to caring adults and peers, have a future orientation, and typically have higher self-esteem. Youth whose parents balance attunement with rules and expectations (“authoritative” parenting) appear to be at lower risk of poor mental health outcomes associated with heavy social media use as well as other risk behaviors. These parents have clear rules and expectations, including about drugs and alcohol, and enforce rules reasonably calmly and consistently. Youth whose families eat dinner together at least three times weekly, who attend schools that offer a wide range of after-school activities, and who learn to use problem-focused coping skills rather than emotion-focused coping skills are protected against poor mental health outcomes in the face of these challenges.
While bullying is a stressor, social media and substances may seem like ways of managing stress and connecting with peers. There are youth with clear vulnerabilities to the risks associated with each of them. Shared factors include vulnerable temperaments, high conflict or permissive parenting, family history of substance use disorders or preexisting psychiatric illness. Pediatricians are in a unique position to raise teenagers’ awareness of their specific vulnerabilities. Talk about the heightened risk of experimentation with alcohol or drugs in your patients who are in treatment for an anxiety or mood disorder. Help them cultivate critical thinking — an adolescent specialty — around marketing and peer pressure. Remind them that social media companies make money from keeping them online longer. Then help them identify what strategies are in their control, such as limiting their time online. What else could they be doing with their time that they actually enjoy? Remind them about the value of protecting time for adequate sleep, regular exercise, and sitting down for dinner with their family. Ask about their nourishing relationships with peers and adults and talk about the value of protecting time for them. Ask your patients and their parents about how they face stress, emphasizing their ability to locate what is within their control. While awareness of feelings is important, learning to manage intense emotions is more connected to healthy habits of sleep and exercise and strategies to get support or pivot to engaging activities. Discussing this openly models for parents how to bear difficulty alongside their children without becoming distressed or punitive themselves. Talk with worried parents about the value of regular meals together, shared physical activities, and supporting time for their children’s emerging interests and hobbies. Equipping your patients and their parents with knowledge about their particular vulnerabilities, reminders about what is known about these risks, and all that is in their power to build resilience, may be as meaningful a public health intervention as asking them about biking with helmets and using seat belts.
Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.
References
1. Zych I et al. Protective Factors Against Bullying and Cyberbullying: A Systematic Review of Meta-Analyses. Aggress Violent Behav. 2019;45:4-19. doi: 10.1016/j.avb.2018.06.008.
2. Office of the Surgeon General. Social Media and Youth Mental Health: The U.S. Surgeon General’s Advisory. 2023. https://www.ncbi.nlm.nih.gov/books/NBK594761/.
3. Uhls Y et al. Benefits and Costs of Social Media in Adolescence. Pediatrics. 2017 Nov;140(Suppl 2):S67-S70. doi: 10.1542/peds.2016-1758E.
4. Health Advisory on Social Media Use in Adolescence. American Psychological Association (2023).
5. Sloboda Z et al. Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention, Substance Use and Misuse, Subst Use Misuse. 2012 Jun-Jul;47(8-9):944-62. doi: 10.3109/10826084.2012.663280.
6. O’Connell M et al. Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press and US Department of Health and Human Services, Substance Abuse and Mental Health Administration. 2009 (https://nap.nationalacademies.org/catalog/12480/preventing-mental-emotional-and-behavioral-disorders-among-young-people-progress).
7. Staiger P et al. Can Emotion-Focused Coping Help Explain the Link Between Posttraumatic Stress Disorder Severity and Triggers for Substance Use in Young Adults? J Subst Abuse Treat. 2009 Mar;36(2):220-6. doi: 10.1016/j.jsat.2008.05.008.
FDA Approves First CAR T-Cell Therapy for rrCLL, rrSLL
Specifically, the CD19-directed chimeric antigen receptor (CAR) T-cell product (Breyanzi) from Juno Therapeutics, a Bristol-Myers Squib company, is approved for adults with CLL or SLL who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. It is the first CAR T-cell therapy approved in this setting.
“CLL and SLL are currently considered incurable diseases with few treatment options in the relapsed setting that can confer complete responses,” lead trial investigator Tanya Siddiqi, MD, of City of Hope in Duarte, California, said in the press release.
The FDA’s approval of liso-cel in this setting “is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission,” Dr. Siddiqi added.
Liso-cel was first approved in 2021 for relapsed or refractory large B-cell lymphoma, as reported at the time by this news organization.
Approval for the new CLL and SLL indication followed Priority Review and was based on findings from the pivotal TRANSCEND CLL 004 study, in which 20% of patients with CLL or SLL achieved a complete response after a one-time liso-cel infusion, according to a Bristol-Myers Squibb press release.
The 89 participants in the open-label, phase 1/2 study received a single dose of liso-cel containing 90-110 x 106CAR-positive viable T cells. The overall response rate was 45%, and median duration of response was 35.3 months. Among the 20% of patients achieving a complete response, the median duration of that response was not reached at the time of data cutoff.
Liso-cel had a tolerable safety profile. Cytokine release syndrome and neurologic events were mostly low grade. Cytokine release syndrome of any grade occurred in 83% of patients; 9% were grade 3, and none were grade 4 or 5.
Neurologic events of any grade occurred in 46% of patients, with grade 3 events occurring in 20% of patients; one grade 4 event and no grade 5 events occurred.
A version of this article appeared on Medscape.com.
Specifically, the CD19-directed chimeric antigen receptor (CAR) T-cell product (Breyanzi) from Juno Therapeutics, a Bristol-Myers Squib company, is approved for adults with CLL or SLL who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. It is the first CAR T-cell therapy approved in this setting.
“CLL and SLL are currently considered incurable diseases with few treatment options in the relapsed setting that can confer complete responses,” lead trial investigator Tanya Siddiqi, MD, of City of Hope in Duarte, California, said in the press release.
The FDA’s approval of liso-cel in this setting “is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission,” Dr. Siddiqi added.
Liso-cel was first approved in 2021 for relapsed or refractory large B-cell lymphoma, as reported at the time by this news organization.
Approval for the new CLL and SLL indication followed Priority Review and was based on findings from the pivotal TRANSCEND CLL 004 study, in which 20% of patients with CLL or SLL achieved a complete response after a one-time liso-cel infusion, according to a Bristol-Myers Squibb press release.
The 89 participants in the open-label, phase 1/2 study received a single dose of liso-cel containing 90-110 x 106CAR-positive viable T cells. The overall response rate was 45%, and median duration of response was 35.3 months. Among the 20% of patients achieving a complete response, the median duration of that response was not reached at the time of data cutoff.
Liso-cel had a tolerable safety profile. Cytokine release syndrome and neurologic events were mostly low grade. Cytokine release syndrome of any grade occurred in 83% of patients; 9% were grade 3, and none were grade 4 or 5.
Neurologic events of any grade occurred in 46% of patients, with grade 3 events occurring in 20% of patients; one grade 4 event and no grade 5 events occurred.
A version of this article appeared on Medscape.com.
Specifically, the CD19-directed chimeric antigen receptor (CAR) T-cell product (Breyanzi) from Juno Therapeutics, a Bristol-Myers Squib company, is approved for adults with CLL or SLL who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. It is the first CAR T-cell therapy approved in this setting.
“CLL and SLL are currently considered incurable diseases with few treatment options in the relapsed setting that can confer complete responses,” lead trial investigator Tanya Siddiqi, MD, of City of Hope in Duarte, California, said in the press release.
The FDA’s approval of liso-cel in this setting “is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission,” Dr. Siddiqi added.
Liso-cel was first approved in 2021 for relapsed or refractory large B-cell lymphoma, as reported at the time by this news organization.
Approval for the new CLL and SLL indication followed Priority Review and was based on findings from the pivotal TRANSCEND CLL 004 study, in which 20% of patients with CLL or SLL achieved a complete response after a one-time liso-cel infusion, according to a Bristol-Myers Squibb press release.
The 89 participants in the open-label, phase 1/2 study received a single dose of liso-cel containing 90-110 x 106CAR-positive viable T cells. The overall response rate was 45%, and median duration of response was 35.3 months. Among the 20% of patients achieving a complete response, the median duration of that response was not reached at the time of data cutoff.
Liso-cel had a tolerable safety profile. Cytokine release syndrome and neurologic events were mostly low grade. Cytokine release syndrome of any grade occurred in 83% of patients; 9% were grade 3, and none were grade 4 or 5.
Neurologic events of any grade occurred in 46% of patients, with grade 3 events occurring in 20% of patients; one grade 4 event and no grade 5 events occurred.
A version of this article appeared on Medscape.com.