As US medical school graduates learned Friday, March 15, where they would spend their residencies, new Match Day 2024 data showed a loss of interest in pediatrics, whereas emergency medicine regained popularity after concern over last year’s unfilled positions.

Hospitals and medical groups offered 41,503 residency positions in 2024, a 3% increase from last year, according to the data released by the National Resident Matching Program. 

Emergency medicine reversed its recent decline, with only 135 unfilled positions, a 13.9% improvement over last year.

But though the number of pediatric residency slots increased slightly from last year, 8% of available positions remained unfilled in 2024 compared with about 3% last year. 

Physician leaders and policymakers alike pay keen attention to Match Day results because they can signal future shortages in certain specialties, including primary care. Unfilled slots also can raise concerns over too many residency programs in a specialty. 

Medical students’ interest in pediatrics continues to decline in part because it pays less than other specialties, Bryan Carmody, MD, MPH, a pediatric nephrologist known for his medical school commentaries, told this news organization. The number of pediatric applicants from US medical schools peaked in 2015 and has fallen since, he said.

“There’s been a lot of soul searching ... this week, with people speculating about lots of (reasons),” Dr. Carmody said. “I don’t think it’s even debt. You can look at the number of unfilled positions, and it correlates with the expected earning potential of those specialties.” 

Family medicine, for example, filled about 88% of its positions this year.

Ob.gyn. residencies retained their popularity despite concerns over abortion and reproductive health rights in many states. The specialty filled 99.6% of its positions, a very slight improvement over last year’s 99% rate. 

Though ob.gyn. applicants might prefer programs in states where there are more liberal policies around reproductive health, many won’t be in a position where they can choose that because of the limited number of ob.gyn. slots, Dr. Carmody said.

Unfilled residency slots likely will be filled through the Supplemental Offer and Acceptance Program (SOAP). Applicants who did not match in the first round participate in SOAP for one of the 2562 positions in 787 programs that went unfilled after the matching algorithm was processed. A total of 2575 positions were placed in SOAP, including positions in programs that did not participate in the algorithm phase of the process. There were 83 fewer positions in SOAP in 2024, a decrease of 3.1% compared with last year’s Match. More detailed data on SOAP results will be released later this year.

A version of this article appeared on Medscape.com.

As US medical school graduates learned Friday, March 15, where they would spend their residencies, new Match Day 2024 data showed a loss of interest in pediatrics, whereas emergency medicine regained popularity after concern over last year’s unfilled positions.

Hospitals and medical groups offered 41,503 residency positions in 2024, a 3% increase from last year, according to the data released by the National Resident Matching Program. 

Emergency medicine reversed its recent decline, with only 135 unfilled positions, a 13.9% improvement over last year.

But though the number of pediatric residency slots increased slightly from last year, 8% of available positions remained unfilled in 2024 compared with about 3% last year. 

Physician leaders and policymakers alike pay keen attention to Match Day results because they can signal future shortages in certain specialties, including primary care. Unfilled slots also can raise concerns over too many residency programs in a specialty. 

Medical students’ interest in pediatrics continues to decline in part because it pays less than other specialties, Bryan Carmody, MD, MPH, a pediatric nephrologist known for his medical school commentaries, told this news organization. The number of pediatric applicants from US medical schools peaked in 2015 and has fallen since, he said.

“There’s been a lot of soul searching ... this week, with people speculating about lots of (reasons),” Dr. Carmody said. “I don’t think it’s even debt. You can look at the number of unfilled positions, and it correlates with the expected earning potential of those specialties.” 

Family medicine, for example, filled about 88% of its positions this year.

Ob.gyn. residencies retained their popularity despite concerns over abortion and reproductive health rights in many states. The specialty filled 99.6% of its positions, a very slight improvement over last year’s 99% rate. 

Though ob.gyn. applicants might prefer programs in states where there are more liberal policies around reproductive health, many won’t be in a position where they can choose that because of the limited number of ob.gyn. slots, Dr. Carmody said.

Unfilled residency slots likely will be filled through the Supplemental Offer and Acceptance Program (SOAP). Applicants who did not match in the first round participate in SOAP for one of the 2562 positions in 787 programs that went unfilled after the matching algorithm was processed. A total of 2575 positions were placed in SOAP, including positions in programs that did not participate in the algorithm phase of the process. There were 83 fewer positions in SOAP in 2024, a decrease of 3.1% compared with last year’s Match. More detailed data on SOAP results will be released later this year.

A version of this article appeared on Medscape.com.

As US medical school graduates learned Friday, March 15, where they would spend their residencies, new Match Day 2024 data showed a loss of interest in pediatrics, whereas emergency medicine regained popularity after concern over last year’s unfilled positions.

Hospitals and medical groups offered 41,503 residency positions in 2024, a 3% increase from last year, according to the data released by the National Resident Matching Program. 

Emergency medicine reversed its recent decline, with only 135 unfilled positions, a 13.9% improvement over last year.

But though the number of pediatric residency slots increased slightly from last year, 8% of available positions remained unfilled in 2024 compared with about 3% last year. 

Physician leaders and policymakers alike pay keen attention to Match Day results because they can signal future shortages in certain specialties, including primary care. Unfilled slots also can raise concerns over too many residency programs in a specialty. 

Medical students’ interest in pediatrics continues to decline in part because it pays less than other specialties, Bryan Carmody, MD, MPH, a pediatric nephrologist known for his medical school commentaries, told this news organization. The number of pediatric applicants from US medical schools peaked in 2015 and has fallen since, he said.

“There’s been a lot of soul searching ... this week, with people speculating about lots of (reasons),” Dr. Carmody said. “I don’t think it’s even debt. You can look at the number of unfilled positions, and it correlates with the expected earning potential of those specialties.” 

Family medicine, for example, filled about 88% of its positions this year.

Ob.gyn. residencies retained their popularity despite concerns over abortion and reproductive health rights in many states. The specialty filled 99.6% of its positions, a very slight improvement over last year’s 99% rate. 

Though ob.gyn. applicants might prefer programs in states where there are more liberal policies around reproductive health, many won’t be in a position where they can choose that because of the limited number of ob.gyn. slots, Dr. Carmody said.

Unfilled residency slots likely will be filled through the Supplemental Offer and Acceptance Program (SOAP). Applicants who did not match in the first round participate in SOAP for one of the 2562 positions in 787 programs that went unfilled after the matching algorithm was processed. A total of 2575 positions were placed in SOAP, including positions in programs that did not participate in the algorithm phase of the process. There were 83 fewer positions in SOAP in 2024, a decrease of 3.1% compared with last year’s Match. More detailed data on SOAP results will be released later this year.

A version of this article appeared on Medscape.com.

WEST PALM BEACH, FLORIDA — An over-the-counter antihistamine that had shown potential for treatment of multiple sclerosis (MS) in animal studies was linked to significant worsening of symptoms in humans, new trial data suggested.

Researchers halted an arm of a clinical trial of clemastine fumarate for MS after a fivefold increase in disease progression was reported in three participants, triggering “stoppage criteria,” investigators said.

The inexpensive antihistamine had been touted as a potential MS treatment following promising early findings, and some patients are reportedly taking it on an off-label basis. It was one of four approved drugs in an ongoing trial led by the National Institute of Allergy and Infectious Diseases (NIAID) to investigate the drugs’ efficacy in the treatment of MS.

“Most patients on the other drugs progressed much slower compared to their baseline,” said senior investigator Bibi Bielekova, MD, with NIAID. “When we compare the results in clemastine arm with all other patients treated with the remaining drugs, the probability that our patients progressed by chance is lower than 0.01%.”

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

TRAP-MS Trial

The OTC antihistamine clemastine has been available for decades under the brand names Tavist and Dayhist. In addition to findings from mouse studies, results from a small clinical trial reported in 2017 suggested that clemastine may promote myelin repair. Other animal studies and another small study with healthy volunteers also suggested the drug may reduce immune activity.

Clemastine fumarate is one of four drugs in the ongoing TRAP-MS phase 1/2 trial, which is sponsored by NIAID. The study is designed to determine what effects, if any, the drugs have on MS biomarkers either alone or in combination.

Other drugs in the study include the diabetes drug pioglitazone (Actos), the muscle relaxant dantrolene (Ryanodex, Revonto, and Dantrium), and the idiopathic pulmonary fibrosis drug pirfenidone (Pirespa).

An estimated 250 adults with MS were expected to be enrolled in the trial, which began in 2017 and is scheduled to reach its primary completion in 2025.

Per the study protocol, nine patients in the clemastine arm were assigned to receive 8 mg/d (divided into three doses of 2, 2, and 4 mg). Cerebrospinal fluid samples were collected at baseline and 6 months after clemastine treatment began.
 

Worsening Symptoms

The three patients whose worsening symptoms triggered stopping criteria when they demonstrated increased disability five times faster than their 18-month baseline, researchers reported.

These participants had increased levels of C-reactive protein and erythrocyte sedimentation rate and gained weight, which study authors said were “suggestive of systemic pro-inflammatory state.”

“We found that clemastine treatment causes significant changes in purinergic metabolism,” lead author Joanna Kocot, PhD, a NIAID fellow, said during the ACTRIMS presentation. “We also confirmed that this toxic effect of clemastine was because of pyroptosis,” a form of cell death.

None of the remaining 55 patients treated with other TRAP-MS therapies triggered safety criteria, which study authors said offered “evidence for clemastine toxicity.”

Demographic information was not provided, but the patients on clemastine with worsening symptoms were older, more disabled, and more obese than the other six patients in the clemastine arm, Dr. Bielekova said during the conference presentation.
 

‘Undesirable’ or ‘Premature’?

Commenting on the findings, Paul J. Tesar, PhD, professor of innovative therapeutics at Case Western Reserve University School of Medicine in Cleveland, said the findings are unexpected.

“Compared to previous trials, the TRAP-MS trial included different patient populations and treated them with clemastine for a longer time period, so it is hard to make direct comparisons,” said Dr. Tesar, who studies MS and did not take part in the new study. “From the limited data disclosed thus far, it does seem likely that clemastine is causing toxicity, possibly through increased inflammation, and accelerating disease progression.”

In the big picture, he said, “while clemastine trials have been important steps toward a first-in-class remyelinating drug, the promiscuous nature of clemastine — it binds to many protein targets — and its known side effects make it undesirable as a mainstay treatment for people with multiple sclerosis.”

Hundreds or perhaps thousands of patients with MS may already take the drug because of the early positive findings, said Ari Green, MD, medical director of the University of California at San Francisco Multiple Sclerosis Center and lead author of the initial 2017 clinical trial on clemastine and myelin repair.

Dr. Green, who was not involved in the new study, said he is skeptical of the findings.

“We can’t conclude much about an effect based on three patients, and the risk that this is a chance effect is extraordinarily high,” he said. “It’s premature to make any attribution of what they saw to clemastine itself.”

Dr. Bielekova disagreed, and said she stands by the findings.

The pyroptosis score, derived from CSF biomarkers, was elevated in MS and higher in progressive MS than in relapsing-remitting MS, she said, adding that pyroptosis correlates with how fast people with MS accumulate disability.

“From all drugs we tested, only clemastine increased this CSF pyroptosis score,” Dr. Bielekova said.

Regardless, Dr. Green urged caution when considering whether to use the drug.

“Nobody should take clemastine without the supervision of a doctor,” he said. “It’s actually best done in the context of clinical trials.”

NIAID funded the study, and the authors had no disclosures. Dr. Tesar is cofounder of Convelo Therapeutics, a biotechnology company developing remyelinating therapeutics for MS. Dr. Green said he is conducting studies related to clemastine, but they do not have industry funding.
 

A version of this article appeared on Medscape.com.

WEST PALM BEACH, FLORIDA — An over-the-counter antihistamine that had shown potential for treatment of multiple sclerosis (MS) in animal studies was linked to significant worsening of symptoms in humans, new trial data suggested.

Researchers halted an arm of a clinical trial of clemastine fumarate for MS after a fivefold increase in disease progression was reported in three participants, triggering “stoppage criteria,” investigators said.

The inexpensive antihistamine had been touted as a potential MS treatment following promising early findings, and some patients are reportedly taking it on an off-label basis. It was one of four approved drugs in an ongoing trial led by the National Institute of Allergy and Infectious Diseases (NIAID) to investigate the drugs’ efficacy in the treatment of MS.

“Most patients on the other drugs progressed much slower compared to their baseline,” said senior investigator Bibi Bielekova, MD, with NIAID. “When we compare the results in clemastine arm with all other patients treated with the remaining drugs, the probability that our patients progressed by chance is lower than 0.01%.”

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

TRAP-MS Trial

The OTC antihistamine clemastine has been available for decades under the brand names Tavist and Dayhist. In addition to findings from mouse studies, results from a small clinical trial reported in 2017 suggested that clemastine may promote myelin repair. Other animal studies and another small study with healthy volunteers also suggested the drug may reduce immune activity.

Clemastine fumarate is one of four drugs in the ongoing TRAP-MS phase 1/2 trial, which is sponsored by NIAID. The study is designed to determine what effects, if any, the drugs have on MS biomarkers either alone or in combination.

Other drugs in the study include the diabetes drug pioglitazone (Actos), the muscle relaxant dantrolene (Ryanodex, Revonto, and Dantrium), and the idiopathic pulmonary fibrosis drug pirfenidone (Pirespa).

An estimated 250 adults with MS were expected to be enrolled in the trial, which began in 2017 and is scheduled to reach its primary completion in 2025.

Per the study protocol, nine patients in the clemastine arm were assigned to receive 8 mg/d (divided into three doses of 2, 2, and 4 mg). Cerebrospinal fluid samples were collected at baseline and 6 months after clemastine treatment began.
 

Worsening Symptoms

The three patients whose worsening symptoms triggered stopping criteria when they demonstrated increased disability five times faster than their 18-month baseline, researchers reported.

These participants had increased levels of C-reactive protein and erythrocyte sedimentation rate and gained weight, which study authors said were “suggestive of systemic pro-inflammatory state.”

“We found that clemastine treatment causes significant changes in purinergic metabolism,” lead author Joanna Kocot, PhD, a NIAID fellow, said during the ACTRIMS presentation. “We also confirmed that this toxic effect of clemastine was because of pyroptosis,” a form of cell death.

None of the remaining 55 patients treated with other TRAP-MS therapies triggered safety criteria, which study authors said offered “evidence for clemastine toxicity.”

Demographic information was not provided, but the patients on clemastine with worsening symptoms were older, more disabled, and more obese than the other six patients in the clemastine arm, Dr. Bielekova said during the conference presentation.
 

‘Undesirable’ or ‘Premature’?

Commenting on the findings, Paul J. Tesar, PhD, professor of innovative therapeutics at Case Western Reserve University School of Medicine in Cleveland, said the findings are unexpected.

“Compared to previous trials, the TRAP-MS trial included different patient populations and treated them with clemastine for a longer time period, so it is hard to make direct comparisons,” said Dr. Tesar, who studies MS and did not take part in the new study. “From the limited data disclosed thus far, it does seem likely that clemastine is causing toxicity, possibly through increased inflammation, and accelerating disease progression.”

In the big picture, he said, “while clemastine trials have been important steps toward a first-in-class remyelinating drug, the promiscuous nature of clemastine — it binds to many protein targets — and its known side effects make it undesirable as a mainstay treatment for people with multiple sclerosis.”

Hundreds or perhaps thousands of patients with MS may already take the drug because of the early positive findings, said Ari Green, MD, medical director of the University of California at San Francisco Multiple Sclerosis Center and lead author of the initial 2017 clinical trial on clemastine and myelin repair.

Dr. Green, who was not involved in the new study, said he is skeptical of the findings.

“We can’t conclude much about an effect based on three patients, and the risk that this is a chance effect is extraordinarily high,” he said. “It’s premature to make any attribution of what they saw to clemastine itself.”

Dr. Bielekova disagreed, and said she stands by the findings.

The pyroptosis score, derived from CSF biomarkers, was elevated in MS and higher in progressive MS than in relapsing-remitting MS, she said, adding that pyroptosis correlates with how fast people with MS accumulate disability.

“From all drugs we tested, only clemastine increased this CSF pyroptosis score,” Dr. Bielekova said.

Regardless, Dr. Green urged caution when considering whether to use the drug.

“Nobody should take clemastine without the supervision of a doctor,” he said. “It’s actually best done in the context of clinical trials.”

NIAID funded the study, and the authors had no disclosures. Dr. Tesar is cofounder of Convelo Therapeutics, a biotechnology company developing remyelinating therapeutics for MS. Dr. Green said he is conducting studies related to clemastine, but they do not have industry funding.
 

A version of this article appeared on Medscape.com.

WEST PALM BEACH, FLORIDA — An over-the-counter antihistamine that had shown potential for treatment of multiple sclerosis (MS) in animal studies was linked to significant worsening of symptoms in humans, new trial data suggested.

Researchers halted an arm of a clinical trial of clemastine fumarate for MS after a fivefold increase in disease progression was reported in three participants, triggering “stoppage criteria,” investigators said.

The inexpensive antihistamine had been touted as a potential MS treatment following promising early findings, and some patients are reportedly taking it on an off-label basis. It was one of four approved drugs in an ongoing trial led by the National Institute of Allergy and Infectious Diseases (NIAID) to investigate the drugs’ efficacy in the treatment of MS.

“Most patients on the other drugs progressed much slower compared to their baseline,” said senior investigator Bibi Bielekova, MD, with NIAID. “When we compare the results in clemastine arm with all other patients treated with the remaining drugs, the probability that our patients progressed by chance is lower than 0.01%.”

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

TRAP-MS Trial

The OTC antihistamine clemastine has been available for decades under the brand names Tavist and Dayhist. In addition to findings from mouse studies, results from a small clinical trial reported in 2017 suggested that clemastine may promote myelin repair. Other animal studies and another small study with healthy volunteers also suggested the drug may reduce immune activity.

Clemastine fumarate is one of four drugs in the ongoing TRAP-MS phase 1/2 trial, which is sponsored by NIAID. The study is designed to determine what effects, if any, the drugs have on MS biomarkers either alone or in combination.

Other drugs in the study include the diabetes drug pioglitazone (Actos), the muscle relaxant dantrolene (Ryanodex, Revonto, and Dantrium), and the idiopathic pulmonary fibrosis drug pirfenidone (Pirespa).

An estimated 250 adults with MS were expected to be enrolled in the trial, which began in 2017 and is scheduled to reach its primary completion in 2025.

Per the study protocol, nine patients in the clemastine arm were assigned to receive 8 mg/d (divided into three doses of 2, 2, and 4 mg). Cerebrospinal fluid samples were collected at baseline and 6 months after clemastine treatment began.
 

Worsening Symptoms

The three patients whose worsening symptoms triggered stopping criteria when they demonstrated increased disability five times faster than their 18-month baseline, researchers reported.

These participants had increased levels of C-reactive protein and erythrocyte sedimentation rate and gained weight, which study authors said were “suggestive of systemic pro-inflammatory state.”

“We found that clemastine treatment causes significant changes in purinergic metabolism,” lead author Joanna Kocot, PhD, a NIAID fellow, said during the ACTRIMS presentation. “We also confirmed that this toxic effect of clemastine was because of pyroptosis,” a form of cell death.

None of the remaining 55 patients treated with other TRAP-MS therapies triggered safety criteria, which study authors said offered “evidence for clemastine toxicity.”

Demographic information was not provided, but the patients on clemastine with worsening symptoms were older, more disabled, and more obese than the other six patients in the clemastine arm, Dr. Bielekova said during the conference presentation.
 

‘Undesirable’ or ‘Premature’?

Commenting on the findings, Paul J. Tesar, PhD, professor of innovative therapeutics at Case Western Reserve University School of Medicine in Cleveland, said the findings are unexpected.

“Compared to previous trials, the TRAP-MS trial included different patient populations and treated them with clemastine for a longer time period, so it is hard to make direct comparisons,” said Dr. Tesar, who studies MS and did not take part in the new study. “From the limited data disclosed thus far, it does seem likely that clemastine is causing toxicity, possibly through increased inflammation, and accelerating disease progression.”

In the big picture, he said, “while clemastine trials have been important steps toward a first-in-class remyelinating drug, the promiscuous nature of clemastine — it binds to many protein targets — and its known side effects make it undesirable as a mainstay treatment for people with multiple sclerosis.”

Hundreds or perhaps thousands of patients with MS may already take the drug because of the early positive findings, said Ari Green, MD, medical director of the University of California at San Francisco Multiple Sclerosis Center and lead author of the initial 2017 clinical trial on clemastine and myelin repair.

Dr. Green, who was not involved in the new study, said he is skeptical of the findings.

“We can’t conclude much about an effect based on three patients, and the risk that this is a chance effect is extraordinarily high,” he said. “It’s premature to make any attribution of what they saw to clemastine itself.”

Dr. Bielekova disagreed, and said she stands by the findings.

The pyroptosis score, derived from CSF biomarkers, was elevated in MS and higher in progressive MS than in relapsing-remitting MS, she said, adding that pyroptosis correlates with how fast people with MS accumulate disability.

“From all drugs we tested, only clemastine increased this CSF pyroptosis score,” Dr. Bielekova said.

Regardless, Dr. Green urged caution when considering whether to use the drug.

“Nobody should take clemastine without the supervision of a doctor,” he said. “It’s actually best done in the context of clinical trials.”

NIAID funded the study, and the authors had no disclosures. Dr. Tesar is cofounder of Convelo Therapeutics, a biotechnology company developing remyelinating therapeutics for MS. Dr. Green said he is conducting studies related to clemastine, but they do not have industry funding.
 

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.

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.

WEST PALM BEACH, CALIFORNIA — Aspirin and acetaminophen may offer an effective and inexpensive solution to exercise-induced heat sensitivity in relapsing-remitting multiple sclerosis (RRMS), 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 — Aspirin and acetaminophen may offer an effective and inexpensive solution to exercise-induced heat sensitivity in relapsing-remitting multiple sclerosis (RRMS), 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 — Aspirin and acetaminophen may offer an effective and inexpensive solution to exercise-induced heat sensitivity in relapsing-remitting multiple sclerosis (RRMS), 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.

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.

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 (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.

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.

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.

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.