Conference Coverage

VANCOUVER, BRITISH COLUMBIA — Family physicians should familiarize themselves with doxycycline post-exposure prophylaxis (doxy PEP) as a prescription for patients who frequently have unprotected sex (including oral, anal, and vaginal) with multiple partners, according to a presentation at the Family Medicine Forum (FMF) 2024. Doxy PEP decreases the risk for bacterial sexually transmitted infections (STIs).

Many family physicians may be unaware of doxy PEP as a means of avoiding STIs. “Doxy PEP is an incredible tool that can be used within 72 hours of unprotected sex to reduce bacterial STI risk,” said James Owen, MD, assistant professor of family and community medicine at the University of Toronto in Ontario, Canada.

The US Centers for Disease Control and Prevention point to data from three randomized, controlled trials that demonstrate the ability of doxy PEP to decrease syphilis and chlamydia infections by more than 70% and decrease gonococcal infections by about 50%, said Jordan Goodridge, MD, assistant professor of family and community medicine at the University of Toronto.

 

Optimizing Doxy PEP

Doxy PEP (200 mg) is most effective when administered in the first 24 hours after unprotected sex, explained Goodridge. It is recommended that patients repeat the 200-mg dose if they are sexually active again within 24 hours.

To ensure optimal absorption of doxy PEP, the drug should not be taken with antacids or multivitamins, said Goodridge. Antacids “can bind to doxycycline and prevent it from being absorbed,” he said.

A key concern about doxy PEP is the development of antimicrobial resistance, noted Goodridge. “We don’t have long-term studies to give us an idea about what this risk is, to quantify it. The studies we have are relatively short, generally less than a year, and didn’t suggest that there was a huge risk [for antimicrobial resistance].”

Moreover, doxycycline is teratogenic, and its use is contraindicated in pregnancy, said Goodridge. If a pregnant patient is being treated for syphilis, then penicillin is the treatment of choice. For pregnant patients with penicillin allergy, Public Health Agency of Canada guidelines call for penicillin desensitization followed by penicillin.

The rate of syphilis has been rising in Canadian women of reproductive age, thus increasing the potential for congenital syphilis, noted Goodridge.

 

Benefits of HPV Vaccine

The 9-valent HPV vaccine is recommended in Canada for patients aged 9-26 years, but those aged 27 years or older at ongoing risk for HPV exposure may receive the 9-valent HPV vaccine after discussion with their healthcare providers, noted Owen.

High-risk patients can benefit from the vaccine even though they have likely had exposure to HPV, he added. “If someone has multiple sexual partners, they have probably been exposed to HPV at some point,” said Owen. “You still could reduce a patient’s risk for being exposed to certain oncogenic strains [of HPV]. Certainly, within our practices, we’re often giving it [that is, the HPV vaccine] to higher-risk individuals, including men having sex with men.”

 

HIV Prevention

“Condoms are still a mainstay of HIV and STI prevention, but condom use is going down,” said Owen.

In a national survey commissioned by the Toronto-based organization LetsStopAIDS and including more than 1100 Canadians aged 18-24 years, 24% of respondents said they use condoms “all the time.” In 2020, by contrast, more than half (53%) of respondents reported that they use condoms all the time.

Updated Canadian guidelines on the use of HIV pre-exposure prophylaxis (PrEP) are expected to be released in 2025 and will address questions about how frequently individuals taking HIV PrEP should be tested to ensure a negative HIV result. The guidelines will also provide guidance as to whether HIV serology or HIV viral load should be captured, said Owen. Patients in Canada who take HIV PrEP are now generally screened for HIV every 3 months.

A new HIV PrEP tool that has become available to Canadian clinicians is the injectable drug cabotegravir, which is dosed every 2 months.

Owen and Goodridge reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — Family physicians should familiarize themselves with doxycycline post-exposure prophylaxis (doxy PEP) as a prescription for patients who frequently have unprotected sex (including oral, anal, and vaginal) with multiple partners, according to a presentation at the Family Medicine Forum (FMF) 2024. Doxy PEP decreases the risk for bacterial sexually transmitted infections (STIs).

Many family physicians may be unaware of doxy PEP as a means of avoiding STIs. “Doxy PEP is an incredible tool that can be used within 72 hours of unprotected sex to reduce bacterial STI risk,” said James Owen, MD, assistant professor of family and community medicine at the University of Toronto in Ontario, Canada.

The US Centers for Disease Control and Prevention point to data from three randomized, controlled trials that demonstrate the ability of doxy PEP to decrease syphilis and chlamydia infections by more than 70% and decrease gonococcal infections by about 50%, said Jordan Goodridge, MD, assistant professor of family and community medicine at the University of Toronto.

 

Optimizing Doxy PEP

Doxy PEP (200 mg) is most effective when administered in the first 24 hours after unprotected sex, explained Goodridge. It is recommended that patients repeat the 200-mg dose if they are sexually active again within 24 hours.

To ensure optimal absorption of doxy PEP, the drug should not be taken with antacids or multivitamins, said Goodridge. Antacids “can bind to doxycycline and prevent it from being absorbed,” he said.

A key concern about doxy PEP is the development of antimicrobial resistance, noted Goodridge. “We don’t have long-term studies to give us an idea about what this risk is, to quantify it. The studies we have are relatively short, generally less than a year, and didn’t suggest that there was a huge risk [for antimicrobial resistance].”

Moreover, doxycycline is teratogenic, and its use is contraindicated in pregnancy, said Goodridge. If a pregnant patient is being treated for syphilis, then penicillin is the treatment of choice. For pregnant patients with penicillin allergy, Public Health Agency of Canada guidelines call for penicillin desensitization followed by penicillin.

The rate of syphilis has been rising in Canadian women of reproductive age, thus increasing the potential for congenital syphilis, noted Goodridge.

 

Benefits of HPV Vaccine

The 9-valent HPV vaccine is recommended in Canada for patients aged 9-26 years, but those aged 27 years or older at ongoing risk for HPV exposure may receive the 9-valent HPV vaccine after discussion with their healthcare providers, noted Owen.

High-risk patients can benefit from the vaccine even though they have likely had exposure to HPV, he added. “If someone has multiple sexual partners, they have probably been exposed to HPV at some point,” said Owen. “You still could reduce a patient’s risk for being exposed to certain oncogenic strains [of HPV]. Certainly, within our practices, we’re often giving it [that is, the HPV vaccine] to higher-risk individuals, including men having sex with men.”

 

HIV Prevention

“Condoms are still a mainstay of HIV and STI prevention, but condom use is going down,” said Owen.

In a national survey commissioned by the Toronto-based organization LetsStopAIDS and including more than 1100 Canadians aged 18-24 years, 24% of respondents said they use condoms “all the time.” In 2020, by contrast, more than half (53%) of respondents reported that they use condoms all the time.

Updated Canadian guidelines on the use of HIV pre-exposure prophylaxis (PrEP) are expected to be released in 2025 and will address questions about how frequently individuals taking HIV PrEP should be tested to ensure a negative HIV result. The guidelines will also provide guidance as to whether HIV serology or HIV viral load should be captured, said Owen. Patients in Canada who take HIV PrEP are now generally screened for HIV every 3 months.

A new HIV PrEP tool that has become available to Canadian clinicians is the injectable drug cabotegravir, which is dosed every 2 months.

Owen and Goodridge reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — Family physicians should familiarize themselves with doxycycline post-exposure prophylaxis (doxy PEP) as a prescription for patients who frequently have unprotected sex (including oral, anal, and vaginal) with multiple partners, according to a presentation at the Family Medicine Forum (FMF) 2024. Doxy PEP decreases the risk for bacterial sexually transmitted infections (STIs).

Many family physicians may be unaware of doxy PEP as a means of avoiding STIs. “Doxy PEP is an incredible tool that can be used within 72 hours of unprotected sex to reduce bacterial STI risk,” said James Owen, MD, assistant professor of family and community medicine at the University of Toronto in Ontario, Canada.

The US Centers for Disease Control and Prevention point to data from three randomized, controlled trials that demonstrate the ability of doxy PEP to decrease syphilis and chlamydia infections by more than 70% and decrease gonococcal infections by about 50%, said Jordan Goodridge, MD, assistant professor of family and community medicine at the University of Toronto.

 

Optimizing Doxy PEP

Doxy PEP (200 mg) is most effective when administered in the first 24 hours after unprotected sex, explained Goodridge. It is recommended that patients repeat the 200-mg dose if they are sexually active again within 24 hours.

To ensure optimal absorption of doxy PEP, the drug should not be taken with antacids or multivitamins, said Goodridge. Antacids “can bind to doxycycline and prevent it from being absorbed,” he said.

A key concern about doxy PEP is the development of antimicrobial resistance, noted Goodridge. “We don’t have long-term studies to give us an idea about what this risk is, to quantify it. The studies we have are relatively short, generally less than a year, and didn’t suggest that there was a huge risk [for antimicrobial resistance].”

Moreover, doxycycline is teratogenic, and its use is contraindicated in pregnancy, said Goodridge. If a pregnant patient is being treated for syphilis, then penicillin is the treatment of choice. For pregnant patients with penicillin allergy, Public Health Agency of Canada guidelines call for penicillin desensitization followed by penicillin.

The rate of syphilis has been rising in Canadian women of reproductive age, thus increasing the potential for congenital syphilis, noted Goodridge.

 

Benefits of HPV Vaccine

The 9-valent HPV vaccine is recommended in Canada for patients aged 9-26 years, but those aged 27 years or older at ongoing risk for HPV exposure may receive the 9-valent HPV vaccine after discussion with their healthcare providers, noted Owen.

High-risk patients can benefit from the vaccine even though they have likely had exposure to HPV, he added. “If someone has multiple sexual partners, they have probably been exposed to HPV at some point,” said Owen. “You still could reduce a patient’s risk for being exposed to certain oncogenic strains [of HPV]. Certainly, within our practices, we’re often giving it [that is, the HPV vaccine] to higher-risk individuals, including men having sex with men.”

 

HIV Prevention

“Condoms are still a mainstay of HIV and STI prevention, but condom use is going down,” said Owen.

In a national survey commissioned by the Toronto-based organization LetsStopAIDS and including more than 1100 Canadians aged 18-24 years, 24% of respondents said they use condoms “all the time.” In 2020, by contrast, more than half (53%) of respondents reported that they use condoms all the time.

Updated Canadian guidelines on the use of HIV pre-exposure prophylaxis (PrEP) are expected to be released in 2025 and will address questions about how frequently individuals taking HIV PrEP should be tested to ensure a negative HIV result. The guidelines will also provide guidance as to whether HIV serology or HIV viral load should be captured, said Owen. Patients in Canada who take HIV PrEP are now generally screened for HIV every 3 months.

A new HIV PrEP tool that has become available to Canadian clinicians is the injectable drug cabotegravir, which is dosed every 2 months.

Owen and Goodridge reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Since the adoption of the most recent Model for End-Stage Liver Disease (MELD 3.0) scoring system by the federal Organ Procurement and Transplantation Network (OPTN) in July 2023, the gender gap in liver transplants has narrowed, according to new research.

In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.

“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California. 

“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). 

 

Changes in MELD and Transplant Numbers

MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium. 

“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong. 

“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported. 

Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added. 

MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy. 

To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.

After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.

In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.

The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong. 

However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.

 

Disparities Continue to Exist 

Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.

“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”

Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity. 

Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.

“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”

In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.

This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said. 

It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”

Kwong, Krag, and Taddei reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Since the adoption of the most recent Model for End-Stage Liver Disease (MELD 3.0) scoring system by the federal Organ Procurement and Transplantation Network (OPTN) in July 2023, the gender gap in liver transplants has narrowed, according to new research.

In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.

“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California. 

“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). 

 

Changes in MELD and Transplant Numbers

MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium. 

“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong. 

“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported. 

Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added. 

MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy. 

To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.

After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.

In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.

The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong. 

However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.

 

Disparities Continue to Exist 

Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.

“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”

Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity. 

Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.

“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”

In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.

This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said. 

It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”

Kwong, Krag, and Taddei reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Since the adoption of the most recent Model for End-Stage Liver Disease (MELD 3.0) scoring system by the federal Organ Procurement and Transplantation Network (OPTN) in July 2023, the gender gap in liver transplants has narrowed, according to new research.

In particular, women are now more likely to be added to the waitlist for a liver transplant, more likely to receive a transplant, and less likely to fall off the waitlist because of death.

“MELD 3.0 improved access to transplantation for women, and now waitlist mortality and transplant rates for women more closely approximate the rates for men,” said lead author Allison Kwong, MD, assistant professor of medicine and transplant hepatologist at Stanford Medicine in California. 

“Overall transplant outcomes have also improved year over year,” said Kwong, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). 

 

Changes in MELD and Transplant Numbers

MELD, which estimates liver failure severity and short-term survival in patients with chronic liver disease, has been used since 2002 to determine organ allocation priority for patients in the United States awaiting liver transplantation. Originally, the score incorporated three variables: creatinine, bilirubin, and the international normalized ratio (INR). MELDNa1, or MELD 2.0, was adopted in 2016 to add sodium. 

“Under this system, however, there have been sex-based disparities” with women receiving lower priority scores despite similar disease severity, said Kwong. 

“This has been attributed to several factors, such as the creatinine term in the MELD score underestimating renal dysfunction in women, height and body size differences, and differences in disease etiology, and how we’ve assigned exception points historically,” she reported. 

Men have had a lower pretransplant mortality rate and higher deceased donor transplant rates, she added. 

MELD 3.0 was developed to address these gender differences and other determinants of waitlist outcomes. The updated equation added 1.33 points for women, as well as adding other variables, such as albumin, interactions between bilirubin and sodium, and interactions between albumin and creatinine, to increase prediction accuracy. 

To observe the effects of the new system, Kwong and colleagues analyzed OPTN data for patients aged 12 years or older, focusing on the records of more than 20,300 newly registered liver transplant candidates, and about 18,700 transplant recipients, during the 12 months before and 12 months after MELD 3.0 was implemented.

After the switch, 43.7% of newly registered liver transplant candidates were women, compared with 40.4% before the switch. At registration, the median age was 55, both before and after the change in policy, and the median MELD score changed from 23 to 22 after implementation.

In addition, 42.1% of transplants occurred among women after MELD 3.0 implementation, as compared with 37.3% before. Overall, deceased donor transplant rates were similar for men and women after MELD 3.0 implementation.

The 90-day waitlist dropout rate — patients who died or became too sick to receive a transplant — decreased from 13.5% to 9.1% among women, which may be partially attributable to MELD 3.0, said Kwong. 

However, waitlist dropout rates also decreased among men, from 9.8% to 7.4%, probably because of improvements in technology, such as machine perfusion, which have increased the number of available livers, she added.

 

Disparities Continue to Exist 

Some disparities still exist. Although the total median MELD score at transplant decreased from 29 to 27, women still had a higher median score of 29 at transplant, compared with a median score of 27 among men.

“This indicates that there may still be differences in transplant access between the sexes,” Kwong said. “There are still body size differences that can affect the probability of transplant, and this would not be addressed by MELD 3.0.”

Additional transplant disparities exist related to other patient characteristics, such as age, race, and ethnicity. 

Future versions of MELD could potentially consider these factors, said session moderator Aleksander Krag, MD, PhD, MBA, professor of clinical medicine at the University of Southern Denmark, Odense, and secretary general of the European Association for the Study of the Liver, 2023-2025.

“There are infinite versions of MELD that can be made,” Kwong said. “It’s still early to see how MELD 3.0 will serve the system, but so far, so good.”

In a comment, Tamar Taddei, MD, professor of medicine in digestive diseases at Yale School of Medicine, New Haven, Connecticut, who comoderated the session, noted the importance of using a MELD score that considers sex-based differences.

This study brings MELD 3.0 to its fruition by reducing the disparities experienced by women who were underserved by the previous scoring systems, she said. 

It was lovely to see that MELD 3.0 reduced the disparities with transplants, and also that the waitlist dropout was reduced — for both men and women,” Taddei said. “This change is a no-brainer.”

Kwong, Krag, and Taddei reported no relevant disclosures.

A version of this article appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.

In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”

 

Curbing Cardiovascular Drugs

The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.

But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.

Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.

“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.

 

Tapering Opioids

Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.

Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”

In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.

Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.

 

Deprescribing Benzodiazepines 

Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.

The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.

Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.

Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.

Young, Kirkwood, and Thomas reported no relevant financial relationships.

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

VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.

In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”

 

Curbing Cardiovascular Drugs

The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.

But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.

Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.

“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.

 

Tapering Opioids

Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.

Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”

In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.

Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.

 

Deprescribing Benzodiazepines 

Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.

The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.

Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.

Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.

Young, Kirkwood, and Thomas reported no relevant financial relationships.

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

VANCOUVER, BRITISH COLUMBIA — While polypharmacy is inevitable for patients with multiple chronic diseases, not all medications improve patient-oriented outcomes, members of the Patients, Experience, Evidence, Research (PEER) team, a group of Canadian primary care professionals who develop evidence-based guidelines, told attendees at the Family Medicine Forum (FMF) 2024.

In a thought-provoking presentation called “Axe the Rx: Deprescribing Chronic Medications with PEER,” the panelists gave examples of medications that may be safely stopped or tapered, particularly for older adults “whose pill bag is heavier than their lunch bag.”

 

Curbing Cardiovascular Drugs

The 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults call for reaching an LDL-C < 1.8 mmol/L in secondary cardiovascular prevention by potentially adding on medical therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors or ezetimibe or both if that target is not reached with the maximal dosage of a statin.

But family physicians do not need to follow this guidance for their patients who have had a myocardial infarction, said Ontario family physician Jennifer Young, MD, a physician advisor in the Canadian College of Family Physicians’ Knowledge Experts and Tools Program.

Treating to below 1.8 mmol/L “means lab testing for the patients,” Young told this news organization. “It means increasing doses [of a statin] to try and get to that level.” If the patient is already on the highest dose of a statin, it means adding other medications that lower cholesterol.

“If that was translating into better outcomes like [preventing] death and another heart attack, then all of that extra effort would be worth it,” said Young. “But we don’t have evidence that it actually does have a benefit for outcomes like death and repeated heart attacks,” compared with putting them on a high dose of a potent statin.

 

Tapering Opioids

Before placing patients on an opioid taper, clinicians should first assess them for opioid use disorder (OUD), said Jessica Kirkwood, MD, assistant professor of family medicine at the University of Alberta in Edmonton, Canada. She suggested using the Prescription Opioid Misuse Index questionnaire to do so.

Clinicians should be much more careful in initiating a taper with patients with OUD, said Kirkwood. They must ensure that these patients are motivated to discontinue their opioids. “We’re losing 21 Canadians a day to the opioid crisis. We all know that cutting someone off their opioids and potentially having them seek opioids elsewhere through illicit means can be fatal.”

In addition, clinicians should spend more time counseling patients with OUD than those without, Kirkwood continued. They must explain to these patients how they are being tapered (eg, the intervals and doses) and highlight the benefits of a taper, such as reduced constipation. Opioid agonist therapy (such as methadone or buprenorphine) can be considered in these patients.

Some research has pointed to the importance of patient motivation as a factor in the success of opioid tapers, noted Kirkwood.

 

Deprescribing Benzodiazepines 

Benzodiazepine receptor agonists, too, often can be deprescribed. These drugs should not be prescribed to promote sleep on a long-term basis. Yet clinicians commonly encounter patients who have been taking them for more than a year, said pharmacist Betsy Thomas, assistant adjunct professor of family medicine at the University of Alberta.

The medications “are usually fairly effective for the first couple of weeks to about a month, and then the benefits start to decrease, and we start to see more harms,” she said.

Some of the harms that have been associated with continued use of benzodiazepine receptor agonists include delayed reaction time and impaired cognition, which can affect the ability to drive, the risk for falls, and the risk for hip fractures, she noted. Some research suggests that these drugs are not an option for treating insomnia in patients aged 65 years or older.

Clinicians should encourage tapering the use of benzodiazepine receptor agonists to minimize dependence and transition patients to nonpharmacologic approaches such as cognitive behavioral therapy to manage insomnia, she said. A recent study demonstrated the efficacy of the intervention, and Thomas suggested that family physicians visit the mysleepwell.ca website for more information.

Young, Kirkwood, and Thomas reported no relevant financial relationships.

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

Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.

Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.

Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.

Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.

There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.

Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways. 

Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine. 

Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said. 

During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.

Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.

Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.

Dodd disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.

Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.

Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.

Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.

There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.

Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways. 

Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine. 

Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said. 

During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.

Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.

Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.

Dodd disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Efforts to combat hyperuricemia may find help from gut microbes, according to Dylan Dodd, MD, PhD, who spoke at the annual research symposium of the Gout, Hyperuricemia, and Crystal-Associated Disease Network.

Dodd is an assistant professor of pathology and microbiology and immunology at Stanford University, Palo Alto, California, where he studies novel metabolic pathways in microbes. “The idea is that we can leverage these novel pathways that microbes have as therapeutics to promote human health, and in particular for this meeting today, we’re focused on hyperuricemia and how microbes that break down purines may actually have a role as urate-lowering therapies,” Dodd said during his presentation.

Specifically, he highlighted the fact that some microbes found in the gut break down purines as a food source, producing both energy and molecular building blocks for their own use. Dietary purines, left intact, can otherwise be absorbed and metabolized by the body to produce urate.

Nucleic acids like DNA and RNA in the diet are first broken down by enzymes produced in the pancreas, resulting in purine nucleosides, which in turn are believed to be the source of purines absorbed in the small intestine and eventually into circulation, according to Dodd. “I really view urate in the intestine as being in equilibrium between being secreted into the lumen but also being reabsorbed, and specifically, as it pertains to microbes in the gut. If the microbes degrade the urate, then it will limit its reabsorption, and that could increase net excretion,” Dodd said.

There is evidence that some strains of Lactobacillus species, which are the most important group in the human gut, can metabolize purine nucleosides, he said. In recent years, researchers have screened for Lactobacillus species capable of metabolizing purine nucleosides. The research shows some strain-to-strain variation, but most are proprietary, making it impossible to conduct follow-up research. A small number of human trials have suggested efficacy, but they have generally been conducted in few patients with mixed results. “Overall, I think it’s promising that these lactobacilli probiotics could potentially be used as urate-lowering therapies,” Dodd said.

Aside from direct metabolism of purines, Dodd’s group has identified an additional pathway that some microbes can use to break down urate into short-chain fatty acids. His group cultured various purine nucleosides with various bacterial strains, including two Lactobacillus strains, under anaerobic conditions. The Lactobacillus strains did not degrade urate, but some bacterial species did. The group also found that Lactobacillus could convert nucleosides, including those derived from purines, into the smaller nucleobase compounds, but they did not consume the resultant purines. Some other types of bacteria consumed all purines “voraciously,” according to Dodd, and his team is working to identify the bacterial genetic pathways that drive the metabolic pathways. 

Such studies may open up various therapeutic pathways, he said. One is to employ Lactobacillus probiotics to convert purine nucleosides to their nucleobases, which could reduce absorption in the small intestine. Other bacteria could potentially be used to convert urate produced by paracellular reabsorption to short-chain fatty acids, which have potential benefits through their anti-inflammatory properties. Finally, probiotics could be engineered to degrade urate produced in the intestine. 

Dodd noted that probiotics would have the advantage of high patient acceptance and are generally regarded as safe. Some existing products might have purine-degrading capabilities but haven’t been tested, he said. However, there is strain-to-strain variation and the probiotic formulas would likely need to be optimized to reduce nucleobases. On the other hand, bacteria that degrade urate are likely safe since they have been found in the guts of healthy individuals. However, there are still potential safety concerns, and it is unknown if they could withstand the harsh conditions of the upper gastrointestinal tract or if they would remain active even in the presence of oxygen found in the small intestine, he said. 

During the Q&A period after his talk, Dodd was asked whether fructose consumption could suppress the function of anaerobic bacteria that naturally degrade purine. “When people talk about fructose-induced hyperuricemia, they talk about the ATP degradation in fructose metabolism in the liver or small intestine, [but] they never talk about this potential pathway in the gut,” the questioner said.

Dodd responded that his group found that some carbohydrates suppress urate degradation in some bacterial strains. “It’s certainly a possible mechanism that increased fructose intake could suppress microbial urate degradation in the gut, and that could contribute to hyperuricemia, but obviously more studies need to be done,” he said.

Another audience member wondered if antibiotic use could be tied to gout risk and whether serum urate levels might rise after antibiotic use. “Do you have any data on serum urate before and after antibiotic use, where you might expect to see changes which might support your hypothesis?” she asked. Dodd said that the group had done a retrospective analysis of data from Stanford’s medical records and did not find a change in serum urate after antibiotic exposure. However, a controlled feeding study of healthy individuals who later received antibiotics showed a large increase in urate levels, but the study did not include plasma samples. “It’s a really good question, and we hope to be able to follow that up,” he said.

Dodd disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

As a doctor with a keen interest in myeloma who is looking ahead to the 2024 American Society of Hematology (ASH) annual meeting December 7-10 in San Diego, I’ve chosen 10 presentations that seem most likely to make the greatest impact on my thinking and practice.

First, let me place my selected studies in context by acknowledging my biases. As a clinician, I’m prone to choosing clinical rather than basic science or translational work — even if translational work might well end up exerting a pivotal impact on practice in the future. And now — in no particular order — here are my picks: 

 

IFM 2017-03 Phase 3 Study 

Frail patients are underrepresented in most myeloma studies, yet in this randomized trial for newly diagnosed myeloma, exclusively frail patients were enrolled. The trial compared daratumumab/lenalidomide to lenalidomide/dexamethasone, and the most recent follow/up shows a progression-free survival (PFS) (48.5 vs 21 months) and overall survival (OS) (not reached vs 36 months) benefit to daratumumab/lenalidomide. What I see in practice is that anti-CD38 monoclonal antibodies are the best-tolerated drugs in this space and should be the backbone of any regimen for frail patients. Steroids should be omitted as early as possible. Future trials may optimize what to give in addition to the anti-CD38 therapy, and how to adapt/escalate therapy to frailty and clinical status, as lenalidomide remains difficult for such patients to tolerate.

AQUILA Study 

This is a randomized, phase 3 comparison of daratumumab to observation for patients with smoldering myeloma. The endpoint was PFS. For context, similar studies done in asymptomatic CLL have shown improved PFS, but not OS, and the authors of such studies have concluded that improvement in PFS alone should not justify a change in approach.

This study shows that daratumumab can improve laboratory markers and reduce progression (60-month PFS rates of 63.1% for daratumumab vs 40.8% with observation). However, several important caveats remain. The protocol only mandated spine/pelvis MRI imaging, not whole-body MRI imaging, and such imaging was only performed once a year, which may not be frequent enough to catch lesions at an earlier stage. These details have important implications, as previous research shows that up to half of lesions can be missed by doing only a spine MRI, as opposed to a whole-body MRI. 

All of this means that had more comprehensive imaging been done, many more patients may have been diagnosed with myeloma. Such patients may have been undertreated, and single agent daratumumab, with a response rate of just 63%, may not have been enough. Conversely, some patients may also have been overtreated using this approach, as the protocol allowed patients who had been diagnosed with smoldering myeloma up to 5 years earlier to be enrolled. Many of these people could have had indolent disease for years prior to enrollment and may not have ever progressed. 

Further information is needed to help us understand this study better. What was the nature of the progression events: asymptomatic lab changes or morbid end organ damage? Was daratumumab given when patients in the control arm progressed to myeloma? My concern is that if patients in the control arm do not universally receive modern daratumumab-containing therapies when they develop myeloma, then an overall survival advantage may be shown simply because patients in the intervention arm are getting a good drug earlier in the disease, while those in the control arm are not getting a good drug at all. Nevertheless, despite these limitations, it is likely this trial will lead to regulatory approval of daratumumab in this space, and lots of discussions from patients and clinicians alike.

 

Extended Follow-Up of Anito-Cel in its First In-Human study 

Two chimeric antigen receptor therapy (CAR-T) products are currently approved for myeloma. Cilta-cel is clearly effective but is associated with problematic late-onset neurological toxicities. Ide-cel appears much less effective. There is clearly a need for a product that is both effective and safe.

Anito-cel has two relevant abstracts this meeting that show much promise. Extended follow-up of anito-cel from its first in human study shows a promising 27-month PFS of 52%, and with no cases of delayed neurotoxicity. I also eagerly await further information from the registrational single-arm study of anti-cel being presented at ASH 2024, which should (hopefully) lead to its accelerated approval.

 

Screening for Myeloma for all People With Vertebral Fractures Likely Unnecessary 

This elegant study of over 9,000 people with vertebral fractures shows that absolute risks for myeloma were 0.43% and 0.63% in women and men with grade 2-3 fractures, respectively, indicating that there is likely little benefit in evaluating asymptomatic individuals with incidentally discovered vertebral fractures for myeloma, unless other features are present. Spread the word.

Further Information on Cevostamab, Another Bispecific Option

We do need effective treatments for targets beyond just BCMA and GPRC5D. Cevostamab, a bispecific targeting FCRH5, represents another option, with updated data on 167 patients. With an overall response rate of 43% (duration of response, 10 months), and a response rate of about 30% in those with prior bispecific exposure, this data helps us contextualize expected benefits as we look forward to the eventual approval of this drug. The efficacy is relatively modest in those who have already progressed on bispecifics, but cevostamab would still be a welcome addition to our arsenal.

Is GPRC5D a Better Target for Car T Rather Than Bispecifics? 

Our currently available GPRC5D bispecific (talquetamab) leads to high rates of skin, oral, and nail toxicity. This drug can also bring significant weight loss. These side effects make me consider that continuous targeting of GPRC5D through a bispecific may not be ideal, and that GPRC5D may be better as a one-time CAR T target. At ASH 2024, we will have 15-month follow-up data from BMS-986393, a GPRC5D CAR T. Response rates for this heavily pretreated population (76% of whom had triple refractory disease) were at 87%, with a median PFS of 14.5 months. Only 6% of patients experienced treatment-related weight loss, and nail (19%), skin (30%), and oral (31%) toxicities were relatively low. I look forward to updated data, as well as data on the resolution of the toxicities seen.

Daratumumab, a Game-Changer for AL Amyloidosis 

A truly effective drug given early can change the natural history of disease, even if patients in the control arm only receive the drug later. A case in point is daratumumab. The 5-year survival rate was 76.1% for the daratumumab/cyclophosphamide/bortezomib/dexamethasone arm and 64.7% for cyclophosphamide/bortezomib/dexamethasone arm. This happened despite the fact that 67% of the control arm patients (among those who received therapy) went on to receive daratumumab later in the disease course.

Understanding how SMM Progresses to MM 

We often hear that we should treat SMM and not just watch carefully because fractures may suddenly happen, or a patient may end up on dialysis. What this retrospective study tells us that amongst 427 patients with SMM, 42 had progression to myeloma, and amongst those 42, only 1 developed renal dysfunction (unclear if this resolved), and only 1 had lytic lesions that were symptomatic. The remainder were all asymptomatic lab and imaging changes. This is a retrospective study, and one should assume that follow-up was thus highly variable. It does not appear that diffusion weighted whole-body MRI imaging (our most sensitive imaging test) was employed universally or very frequently. Nevertheless, these powerful findings reassure us that, with close observation, morbidity is unlikely. Our group has designed a prospective study incorporating frequent diffusion weighted whole body MRI imaging to formally test this hypothesis (SPOTLIGHT, NCT06212323). 

The Underperformance of Daratumumab/Lenalidomide/Dexamethasone in the Real World 

At every major meeting I am reminded of the disconnect between real-world efficacy and clinical trial efficacy. Case in point: In this Austrian experience, daratumumab/lenalidomide/dexamethasone led to a PFS of 22.7 months vs 61.9 months in the MAIA trial of daratumumab/lenalidomide/dexamethasone. Such a sobering difference! And if you think this is an isolated experience, even in a US real-world cohort, consider that in a recently published comparative study dara/len/dex underperformed, although the time to next treatment or death was longer (37.8 months).

Delayed Neurotoxicity may not be Just a Consequence of high tumor burden 

We currently think that some of the scariest side effects of cilta-cel, such as delayed neurotoxicity, may be a consequence of a high number of cancer cells and may be prevented by better disease control at the time of infusion. This study, a sobering analysis of 52 patients with delayed neurotoxicity occurring after CAR T, included 8 patients (15%) who were not heavily pretreated, and all had less than 5% plasma cells at the time of infusion. None of these patients had extramedullary disease. This result worries me, especially because cilta-cel is being studied and is poised for future approval in earlier line settings. It suggests that this toxicity may not always be a product of disease burden, contrary to our current belief.

I will be paying close attention to these 10 myeloma studies at ASH 2024, where I look forward to meeting you and learning more.Dr. Mohyuddin is assistant professor in the multiple myeloma program at the Huntsman Cancer Institute at the University of Utah, Salt Lake City.

As a doctor with a keen interest in myeloma who is looking ahead to the 2024 American Society of Hematology (ASH) annual meeting December 7-10 in San Diego, I’ve chosen 10 presentations that seem most likely to make the greatest impact on my thinking and practice.

First, let me place my selected studies in context by acknowledging my biases. As a clinician, I’m prone to choosing clinical rather than basic science or translational work — even if translational work might well end up exerting a pivotal impact on practice in the future. And now — in no particular order — here are my picks: 

 

IFM 2017-03 Phase 3 Study 

Frail patients are underrepresented in most myeloma studies, yet in this randomized trial for newly diagnosed myeloma, exclusively frail patients were enrolled. The trial compared daratumumab/lenalidomide to lenalidomide/dexamethasone, and the most recent follow/up shows a progression-free survival (PFS) (48.5 vs 21 months) and overall survival (OS) (not reached vs 36 months) benefit to daratumumab/lenalidomide. What I see in practice is that anti-CD38 monoclonal antibodies are the best-tolerated drugs in this space and should be the backbone of any regimen for frail patients. Steroids should be omitted as early as possible. Future trials may optimize what to give in addition to the anti-CD38 therapy, and how to adapt/escalate therapy to frailty and clinical status, as lenalidomide remains difficult for such patients to tolerate.

AQUILA Study 

This is a randomized, phase 3 comparison of daratumumab to observation for patients with smoldering myeloma. The endpoint was PFS. For context, similar studies done in asymptomatic CLL have shown improved PFS, but not OS, and the authors of such studies have concluded that improvement in PFS alone should not justify a change in approach.

This study shows that daratumumab can improve laboratory markers and reduce progression (60-month PFS rates of 63.1% for daratumumab vs 40.8% with observation). However, several important caveats remain. The protocol only mandated spine/pelvis MRI imaging, not whole-body MRI imaging, and such imaging was only performed once a year, which may not be frequent enough to catch lesions at an earlier stage. These details have important implications, as previous research shows that up to half of lesions can be missed by doing only a spine MRI, as opposed to a whole-body MRI. 

All of this means that had more comprehensive imaging been done, many more patients may have been diagnosed with myeloma. Such patients may have been undertreated, and single agent daratumumab, with a response rate of just 63%, may not have been enough. Conversely, some patients may also have been overtreated using this approach, as the protocol allowed patients who had been diagnosed with smoldering myeloma up to 5 years earlier to be enrolled. Many of these people could have had indolent disease for years prior to enrollment and may not have ever progressed. 

Further information is needed to help us understand this study better. What was the nature of the progression events: asymptomatic lab changes or morbid end organ damage? Was daratumumab given when patients in the control arm progressed to myeloma? My concern is that if patients in the control arm do not universally receive modern daratumumab-containing therapies when they develop myeloma, then an overall survival advantage may be shown simply because patients in the intervention arm are getting a good drug earlier in the disease, while those in the control arm are not getting a good drug at all. Nevertheless, despite these limitations, it is likely this trial will lead to regulatory approval of daratumumab in this space, and lots of discussions from patients and clinicians alike.

 

Extended Follow-Up of Anito-Cel in its First In-Human study 

Two chimeric antigen receptor therapy (CAR-T) products are currently approved for myeloma. Cilta-cel is clearly effective but is associated with problematic late-onset neurological toxicities. Ide-cel appears much less effective. There is clearly a need for a product that is both effective and safe.

Anito-cel has two relevant abstracts this meeting that show much promise. Extended follow-up of anito-cel from its first in human study shows a promising 27-month PFS of 52%, and with no cases of delayed neurotoxicity. I also eagerly await further information from the registrational single-arm study of anti-cel being presented at ASH 2024, which should (hopefully) lead to its accelerated approval.

 

Screening for Myeloma for all People With Vertebral Fractures Likely Unnecessary 

This elegant study of over 9,000 people with vertebral fractures shows that absolute risks for myeloma were 0.43% and 0.63% in women and men with grade 2-3 fractures, respectively, indicating that there is likely little benefit in evaluating asymptomatic individuals with incidentally discovered vertebral fractures for myeloma, unless other features are present. Spread the word.

Further Information on Cevostamab, Another Bispecific Option

We do need effective treatments for targets beyond just BCMA and GPRC5D. Cevostamab, a bispecific targeting FCRH5, represents another option, with updated data on 167 patients. With an overall response rate of 43% (duration of response, 10 months), and a response rate of about 30% in those with prior bispecific exposure, this data helps us contextualize expected benefits as we look forward to the eventual approval of this drug. The efficacy is relatively modest in those who have already progressed on bispecifics, but cevostamab would still be a welcome addition to our arsenal.

Is GPRC5D a Better Target for Car T Rather Than Bispecifics? 

Our currently available GPRC5D bispecific (talquetamab) leads to high rates of skin, oral, and nail toxicity. This drug can also bring significant weight loss. These side effects make me consider that continuous targeting of GPRC5D through a bispecific may not be ideal, and that GPRC5D may be better as a one-time CAR T target. At ASH 2024, we will have 15-month follow-up data from BMS-986393, a GPRC5D CAR T. Response rates for this heavily pretreated population (76% of whom had triple refractory disease) were at 87%, with a median PFS of 14.5 months. Only 6% of patients experienced treatment-related weight loss, and nail (19%), skin (30%), and oral (31%) toxicities were relatively low. I look forward to updated data, as well as data on the resolution of the toxicities seen.

Daratumumab, a Game-Changer for AL Amyloidosis 

A truly effective drug given early can change the natural history of disease, even if patients in the control arm only receive the drug later. A case in point is daratumumab. The 5-year survival rate was 76.1% for the daratumumab/cyclophosphamide/bortezomib/dexamethasone arm and 64.7% for cyclophosphamide/bortezomib/dexamethasone arm. This happened despite the fact that 67% of the control arm patients (among those who received therapy) went on to receive daratumumab later in the disease course.

Understanding how SMM Progresses to MM 

We often hear that we should treat SMM and not just watch carefully because fractures may suddenly happen, or a patient may end up on dialysis. What this retrospective study tells us that amongst 427 patients with SMM, 42 had progression to myeloma, and amongst those 42, only 1 developed renal dysfunction (unclear if this resolved), and only 1 had lytic lesions that were symptomatic. The remainder were all asymptomatic lab and imaging changes. This is a retrospective study, and one should assume that follow-up was thus highly variable. It does not appear that diffusion weighted whole-body MRI imaging (our most sensitive imaging test) was employed universally or very frequently. Nevertheless, these powerful findings reassure us that, with close observation, morbidity is unlikely. Our group has designed a prospective study incorporating frequent diffusion weighted whole body MRI imaging to formally test this hypothesis (SPOTLIGHT, NCT06212323). 

The Underperformance of Daratumumab/Lenalidomide/Dexamethasone in the Real World 

At every major meeting I am reminded of the disconnect between real-world efficacy and clinical trial efficacy. Case in point: In this Austrian experience, daratumumab/lenalidomide/dexamethasone led to a PFS of 22.7 months vs 61.9 months in the MAIA trial of daratumumab/lenalidomide/dexamethasone. Such a sobering difference! And if you think this is an isolated experience, even in a US real-world cohort, consider that in a recently published comparative study dara/len/dex underperformed, although the time to next treatment or death was longer (37.8 months).

Delayed Neurotoxicity may not be Just a Consequence of high tumor burden 

We currently think that some of the scariest side effects of cilta-cel, such as delayed neurotoxicity, may be a consequence of a high number of cancer cells and may be prevented by better disease control at the time of infusion. This study, a sobering analysis of 52 patients with delayed neurotoxicity occurring after CAR T, included 8 patients (15%) who were not heavily pretreated, and all had less than 5% plasma cells at the time of infusion. None of these patients had extramedullary disease. This result worries me, especially because cilta-cel is being studied and is poised for future approval in earlier line settings. It suggests that this toxicity may not always be a product of disease burden, contrary to our current belief.

I will be paying close attention to these 10 myeloma studies at ASH 2024, where I look forward to meeting you and learning more.Dr. Mohyuddin is assistant professor in the multiple myeloma program at the Huntsman Cancer Institute at the University of Utah, Salt Lake City.

As a doctor with a keen interest in myeloma who is looking ahead to the 2024 American Society of Hematology (ASH) annual meeting December 7-10 in San Diego, I’ve chosen 10 presentations that seem most likely to make the greatest impact on my thinking and practice.

First, let me place my selected studies in context by acknowledging my biases. As a clinician, I’m prone to choosing clinical rather than basic science or translational work — even if translational work might well end up exerting a pivotal impact on practice in the future. And now — in no particular order — here are my picks: 

 

IFM 2017-03 Phase 3 Study 

Frail patients are underrepresented in most myeloma studies, yet in this randomized trial for newly diagnosed myeloma, exclusively frail patients were enrolled. The trial compared daratumumab/lenalidomide to lenalidomide/dexamethasone, and the most recent follow/up shows a progression-free survival (PFS) (48.5 vs 21 months) and overall survival (OS) (not reached vs 36 months) benefit to daratumumab/lenalidomide. What I see in practice is that anti-CD38 monoclonal antibodies are the best-tolerated drugs in this space and should be the backbone of any regimen for frail patients. Steroids should be omitted as early as possible. Future trials may optimize what to give in addition to the anti-CD38 therapy, and how to adapt/escalate therapy to frailty and clinical status, as lenalidomide remains difficult for such patients to tolerate.

AQUILA Study 

This is a randomized, phase 3 comparison of daratumumab to observation for patients with smoldering myeloma. The endpoint was PFS. For context, similar studies done in asymptomatic CLL have shown improved PFS, but not OS, and the authors of such studies have concluded that improvement in PFS alone should not justify a change in approach.

This study shows that daratumumab can improve laboratory markers and reduce progression (60-month PFS rates of 63.1% for daratumumab vs 40.8% with observation). However, several important caveats remain. The protocol only mandated spine/pelvis MRI imaging, not whole-body MRI imaging, and such imaging was only performed once a year, which may not be frequent enough to catch lesions at an earlier stage. These details have important implications, as previous research shows that up to half of lesions can be missed by doing only a spine MRI, as opposed to a whole-body MRI. 

All of this means that had more comprehensive imaging been done, many more patients may have been diagnosed with myeloma. Such patients may have been undertreated, and single agent daratumumab, with a response rate of just 63%, may not have been enough. Conversely, some patients may also have been overtreated using this approach, as the protocol allowed patients who had been diagnosed with smoldering myeloma up to 5 years earlier to be enrolled. Many of these people could have had indolent disease for years prior to enrollment and may not have ever progressed. 

Further information is needed to help us understand this study better. What was the nature of the progression events: asymptomatic lab changes or morbid end organ damage? Was daratumumab given when patients in the control arm progressed to myeloma? My concern is that if patients in the control arm do not universally receive modern daratumumab-containing therapies when they develop myeloma, then an overall survival advantage may be shown simply because patients in the intervention arm are getting a good drug earlier in the disease, while those in the control arm are not getting a good drug at all. Nevertheless, despite these limitations, it is likely this trial will lead to regulatory approval of daratumumab in this space, and lots of discussions from patients and clinicians alike.

 

Extended Follow-Up of Anito-Cel in its First In-Human study 

Two chimeric antigen receptor therapy (CAR-T) products are currently approved for myeloma. Cilta-cel is clearly effective but is associated with problematic late-onset neurological toxicities. Ide-cel appears much less effective. There is clearly a need for a product that is both effective and safe.

Anito-cel has two relevant abstracts this meeting that show much promise. Extended follow-up of anito-cel from its first in human study shows a promising 27-month PFS of 52%, and with no cases of delayed neurotoxicity. I also eagerly await further information from the registrational single-arm study of anti-cel being presented at ASH 2024, which should (hopefully) lead to its accelerated approval.

 

Screening for Myeloma for all People With Vertebral Fractures Likely Unnecessary 

This elegant study of over 9,000 people with vertebral fractures shows that absolute risks for myeloma were 0.43% and 0.63% in women and men with grade 2-3 fractures, respectively, indicating that there is likely little benefit in evaluating asymptomatic individuals with incidentally discovered vertebral fractures for myeloma, unless other features are present. Spread the word.

Further Information on Cevostamab, Another Bispecific Option

We do need effective treatments for targets beyond just BCMA and GPRC5D. Cevostamab, a bispecific targeting FCRH5, represents another option, with updated data on 167 patients. With an overall response rate of 43% (duration of response, 10 months), and a response rate of about 30% in those with prior bispecific exposure, this data helps us contextualize expected benefits as we look forward to the eventual approval of this drug. The efficacy is relatively modest in those who have already progressed on bispecifics, but cevostamab would still be a welcome addition to our arsenal.

Is GPRC5D a Better Target for Car T Rather Than Bispecifics? 

Our currently available GPRC5D bispecific (talquetamab) leads to high rates of skin, oral, and nail toxicity. This drug can also bring significant weight loss. These side effects make me consider that continuous targeting of GPRC5D through a bispecific may not be ideal, and that GPRC5D may be better as a one-time CAR T target. At ASH 2024, we will have 15-month follow-up data from BMS-986393, a GPRC5D CAR T. Response rates for this heavily pretreated population (76% of whom had triple refractory disease) were at 87%, with a median PFS of 14.5 months. Only 6% of patients experienced treatment-related weight loss, and nail (19%), skin (30%), and oral (31%) toxicities were relatively low. I look forward to updated data, as well as data on the resolution of the toxicities seen.

Daratumumab, a Game-Changer for AL Amyloidosis 

A truly effective drug given early can change the natural history of disease, even if patients in the control arm only receive the drug later. A case in point is daratumumab. The 5-year survival rate was 76.1% for the daratumumab/cyclophosphamide/bortezomib/dexamethasone arm and 64.7% for cyclophosphamide/bortezomib/dexamethasone arm. This happened despite the fact that 67% of the control arm patients (among those who received therapy) went on to receive daratumumab later in the disease course.

Understanding how SMM Progresses to MM 

We often hear that we should treat SMM and not just watch carefully because fractures may suddenly happen, or a patient may end up on dialysis. What this retrospective study tells us that amongst 427 patients with SMM, 42 had progression to myeloma, and amongst those 42, only 1 developed renal dysfunction (unclear if this resolved), and only 1 had lytic lesions that were symptomatic. The remainder were all asymptomatic lab and imaging changes. This is a retrospective study, and one should assume that follow-up was thus highly variable. It does not appear that diffusion weighted whole-body MRI imaging (our most sensitive imaging test) was employed universally or very frequently. Nevertheless, these powerful findings reassure us that, with close observation, morbidity is unlikely. Our group has designed a prospective study incorporating frequent diffusion weighted whole body MRI imaging to formally test this hypothesis (SPOTLIGHT, NCT06212323). 

The Underperformance of Daratumumab/Lenalidomide/Dexamethasone in the Real World 

At every major meeting I am reminded of the disconnect between real-world efficacy and clinical trial efficacy. Case in point: In this Austrian experience, daratumumab/lenalidomide/dexamethasone led to a PFS of 22.7 months vs 61.9 months in the MAIA trial of daratumumab/lenalidomide/dexamethasone. Such a sobering difference! And if you think this is an isolated experience, even in a US real-world cohort, consider that in a recently published comparative study dara/len/dex underperformed, although the time to next treatment or death was longer (37.8 months).

Delayed Neurotoxicity may not be Just a Consequence of high tumor burden 

We currently think that some of the scariest side effects of cilta-cel, such as delayed neurotoxicity, may be a consequence of a high number of cancer cells and may be prevented by better disease control at the time of infusion. This study, a sobering analysis of 52 patients with delayed neurotoxicity occurring after CAR T, included 8 patients (15%) who were not heavily pretreated, and all had less than 5% plasma cells at the time of infusion. None of these patients had extramedullary disease. This result worries me, especially because cilta-cel is being studied and is poised for future approval in earlier line settings. It suggests that this toxicity may not always be a product of disease burden, contrary to our current belief.

I will be paying close attention to these 10 myeloma studies at ASH 2024, where I look forward to meeting you and learning more.Dr. Mohyuddin is assistant professor in the multiple myeloma program at the Huntsman Cancer Institute at the University of Utah, Salt Lake City.

LAS VEGAS — When patients with rosacea consult Julie C. Harper, MD, about persistent facial erythema, she often recommends brimonidine 0.33% gel or oxymetazoline 1% cream.

These agents “work fast” and “improve redness quickly,” Harper, a dermatologist who practices in Birmingham, Alabama, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. In addition, “you’re going to know within 30 minutes or an hour whether it’s going to work or not.”

Brimonidine 0.33% gel, an alpha-2 adrenergic receptor agonist, was approved by the Food and Drug Administration (FDA) in 2014 for persistent facial erythema of rosacea. It does not treat telangiectasia and is not approved for flushing (transient erythema). Patients are advised to apply the gel daily in the morning. In phase 3 pivotal trials of patients with moderate to severe erythema of rosacea, which excluded individuals with more than two papules, a composite (investigator- and patient-reported) 2-grade improvement was seen as early as 30 minutes after application on day 1, and erythema was reduced for 9-12 hours.

Oxymetazoline 1% cream, an alpha-1a adrenergic receptor agonist, was approved by the FDA in 2017 for persistent facial erythema of rosacea. It neither treats telangiectasia nor is approved for flushing. Phase 3 trials of patients with moderate to severe persistent erythema of rosacea excluded individuals with more than three inflammatory papules or pustules. A composite (investigator- and subject-reported) 2-grade improvement was seen as early as 1 hour after application on day 1, and erythema was reduced for 9-12 hours.

 

Receptor Selectivity Differences

According to Harper, there are more reports of worsening erythema with brimonidine 0.33% gel than with oxymetazoline 1% cream, perhaps because of the different receptor selectivity between the two products. She explained that alpha-1 receptors are located only postsynaptically in vascular smooth muscle, while alpha-2 receptors are located presynaptically, which can inhibit norepinephrine and lead to vasodilation. Alpha-2 receptors are also located postsynaptically in vascular smooth muscle and in the endothelial wall, which can mediate nitric oxide release and cause vasodilation.

No head-to-head studies exist that compare brimonidine 0.33% gel with oxymetazoline 1% cream. But in a 52-week study of oxymetazoline 1% cream for persistent facial erythema associated with rosacea published in 2018, at week 52, 36.7% and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Also, fewer than 1% of patients experienced a rebound effect following treatment cessation.

“What we learned from this study is that maybe patients do better if they use oxymetazoline 1% cream consistently,” Harper said. “Does that mean that everybody I give this to uses it daily? Probably not, but I think we can change the vascular tone by using it consistently every day.”

 

Oral Beta-Blockers Another Option

Alpha agonists can also help quell flushing associated with rosacea, Harper continued, but oral beta-blockers may be the better choice. In a 2020 review that drew from nine studies, researchers evaluated the use of carvedilol, propranolol, nadolol, and beta-blockers in general for rosacea-associated facial erythema and flushing. Articles studying carvedilol and propranolol showed a large reduction of erythema and flushing during treatment with a rapid onset of symptom control, while bradycardia and hypotension were the most commonly reported adverse events. “All of these agents are studied in rosacea, but none of them are FDA approved for rosacea,” Harper noted.

In a separate study, five patients with rosacea who had either severe frequent flushing episodes or persistent erythema and burning sensations were treated with carvedilol, a nonselective beta-blocker. Prior treatments included cetirizine and doxycycline, or isotretinoin combined with topical application of metronidazole gel or ivermectin without sufficient improvement in erythema. Carvedilol was added to the above treatments and titrated up to 12.5 mg twice a day and continued for at least 6 months.

The Clinician Erythema Assessment 5-point scale before therapy was 3.4 and dropped to 0.4 during therapy, while the patient self-assessment before therapy was 3.8 and dropped to 0.8 during therapy.

Another study evaluated the use of propranolol and/or doxycycline in 78 patients with rosacea. The propranolol and combination treatment groups showed more rapid improvement at weeks 4 and 8, but there was no statistically significant difference between them by week 12. Rosacea clinical scores also decreased in all groups, but there were no significant differences between them. Reduction of Assessment of Rosacea Clinical Score was 51%, 52.2%, and 57.3% in the propranolol, doxycycline, and combination groups, respectively.

Harper disclosed ties with Almirall, Cutera, Galderma, Journey, Ortho Dermatologics, and Sun Pharmaceutical Industries.

A version of this article appeared on Medscape.com.

LAS VEGAS — When patients with rosacea consult Julie C. Harper, MD, about persistent facial erythema, she often recommends brimonidine 0.33% gel or oxymetazoline 1% cream.

These agents “work fast” and “improve redness quickly,” Harper, a dermatologist who practices in Birmingham, Alabama, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. In addition, “you’re going to know within 30 minutes or an hour whether it’s going to work or not.”

Brimonidine 0.33% gel, an alpha-2 adrenergic receptor agonist, was approved by the Food and Drug Administration (FDA) in 2014 for persistent facial erythema of rosacea. It does not treat telangiectasia and is not approved for flushing (transient erythema). Patients are advised to apply the gel daily in the morning. In phase 3 pivotal trials of patients with moderate to severe erythema of rosacea, which excluded individuals with more than two papules, a composite (investigator- and patient-reported) 2-grade improvement was seen as early as 30 minutes after application on day 1, and erythema was reduced for 9-12 hours.

Oxymetazoline 1% cream, an alpha-1a adrenergic receptor agonist, was approved by the FDA in 2017 for persistent facial erythema of rosacea. It neither treats telangiectasia nor is approved for flushing. Phase 3 trials of patients with moderate to severe persistent erythema of rosacea excluded individuals with more than three inflammatory papules or pustules. A composite (investigator- and subject-reported) 2-grade improvement was seen as early as 1 hour after application on day 1, and erythema was reduced for 9-12 hours.

 

Receptor Selectivity Differences

According to Harper, there are more reports of worsening erythema with brimonidine 0.33% gel than with oxymetazoline 1% cream, perhaps because of the different receptor selectivity between the two products. She explained that alpha-1 receptors are located only postsynaptically in vascular smooth muscle, while alpha-2 receptors are located presynaptically, which can inhibit norepinephrine and lead to vasodilation. Alpha-2 receptors are also located postsynaptically in vascular smooth muscle and in the endothelial wall, which can mediate nitric oxide release and cause vasodilation.

No head-to-head studies exist that compare brimonidine 0.33% gel with oxymetazoline 1% cream. But in a 52-week study of oxymetazoline 1% cream for persistent facial erythema associated with rosacea published in 2018, at week 52, 36.7% and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Also, fewer than 1% of patients experienced a rebound effect following treatment cessation.

“What we learned from this study is that maybe patients do better if they use oxymetazoline 1% cream consistently,” Harper said. “Does that mean that everybody I give this to uses it daily? Probably not, but I think we can change the vascular tone by using it consistently every day.”

 

Oral Beta-Blockers Another Option

Alpha agonists can also help quell flushing associated with rosacea, Harper continued, but oral beta-blockers may be the better choice. In a 2020 review that drew from nine studies, researchers evaluated the use of carvedilol, propranolol, nadolol, and beta-blockers in general for rosacea-associated facial erythema and flushing. Articles studying carvedilol and propranolol showed a large reduction of erythema and flushing during treatment with a rapid onset of symptom control, while bradycardia and hypotension were the most commonly reported adverse events. “All of these agents are studied in rosacea, but none of them are FDA approved for rosacea,” Harper noted.

In a separate study, five patients with rosacea who had either severe frequent flushing episodes or persistent erythema and burning sensations were treated with carvedilol, a nonselective beta-blocker. Prior treatments included cetirizine and doxycycline, or isotretinoin combined with topical application of metronidazole gel or ivermectin without sufficient improvement in erythema. Carvedilol was added to the above treatments and titrated up to 12.5 mg twice a day and continued for at least 6 months.

The Clinician Erythema Assessment 5-point scale before therapy was 3.4 and dropped to 0.4 during therapy, while the patient self-assessment before therapy was 3.8 and dropped to 0.8 during therapy.

Another study evaluated the use of propranolol and/or doxycycline in 78 patients with rosacea. The propranolol and combination treatment groups showed more rapid improvement at weeks 4 and 8, but there was no statistically significant difference between them by week 12. Rosacea clinical scores also decreased in all groups, but there were no significant differences between them. Reduction of Assessment of Rosacea Clinical Score was 51%, 52.2%, and 57.3% in the propranolol, doxycycline, and combination groups, respectively.

Harper disclosed ties with Almirall, Cutera, Galderma, Journey, Ortho Dermatologics, and Sun Pharmaceutical Industries.

A version of this article appeared on Medscape.com.

LAS VEGAS — When patients with rosacea consult Julie C. Harper, MD, about persistent facial erythema, she often recommends brimonidine 0.33% gel or oxymetazoline 1% cream.

These agents “work fast” and “improve redness quickly,” Harper, a dermatologist who practices in Birmingham, Alabama, said at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. In addition, “you’re going to know within 30 minutes or an hour whether it’s going to work or not.”

Brimonidine 0.33% gel, an alpha-2 adrenergic receptor agonist, was approved by the Food and Drug Administration (FDA) in 2014 for persistent facial erythema of rosacea. It does not treat telangiectasia and is not approved for flushing (transient erythema). Patients are advised to apply the gel daily in the morning. In phase 3 pivotal trials of patients with moderate to severe erythema of rosacea, which excluded individuals with more than two papules, a composite (investigator- and patient-reported) 2-grade improvement was seen as early as 30 minutes after application on day 1, and erythema was reduced for 9-12 hours.

Oxymetazoline 1% cream, an alpha-1a adrenergic receptor agonist, was approved by the FDA in 2017 for persistent facial erythema of rosacea. It neither treats telangiectasia nor is approved for flushing. Phase 3 trials of patients with moderate to severe persistent erythema of rosacea excluded individuals with more than three inflammatory papules or pustules. A composite (investigator- and subject-reported) 2-grade improvement was seen as early as 1 hour after application on day 1, and erythema was reduced for 9-12 hours.

 

Receptor Selectivity Differences

According to Harper, there are more reports of worsening erythema with brimonidine 0.33% gel than with oxymetazoline 1% cream, perhaps because of the different receptor selectivity between the two products. She explained that alpha-1 receptors are located only postsynaptically in vascular smooth muscle, while alpha-2 receptors are located presynaptically, which can inhibit norepinephrine and lead to vasodilation. Alpha-2 receptors are also located postsynaptically in vascular smooth muscle and in the endothelial wall, which can mediate nitric oxide release and cause vasodilation.

No head-to-head studies exist that compare brimonidine 0.33% gel with oxymetazoline 1% cream. But in a 52-week study of oxymetazoline 1% cream for persistent facial erythema associated with rosacea published in 2018, at week 52, 36.7% and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Also, fewer than 1% of patients experienced a rebound effect following treatment cessation.

“What we learned from this study is that maybe patients do better if they use oxymetazoline 1% cream consistently,” Harper said. “Does that mean that everybody I give this to uses it daily? Probably not, but I think we can change the vascular tone by using it consistently every day.”

 

Oral Beta-Blockers Another Option

Alpha agonists can also help quell flushing associated with rosacea, Harper continued, but oral beta-blockers may be the better choice. In a 2020 review that drew from nine studies, researchers evaluated the use of carvedilol, propranolol, nadolol, and beta-blockers in general for rosacea-associated facial erythema and flushing. Articles studying carvedilol and propranolol showed a large reduction of erythema and flushing during treatment with a rapid onset of symptom control, while bradycardia and hypotension were the most commonly reported adverse events. “All of these agents are studied in rosacea, but none of them are FDA approved for rosacea,” Harper noted.

In a separate study, five patients with rosacea who had either severe frequent flushing episodes or persistent erythema and burning sensations were treated with carvedilol, a nonselective beta-blocker. Prior treatments included cetirizine and doxycycline, or isotretinoin combined with topical application of metronidazole gel or ivermectin without sufficient improvement in erythema. Carvedilol was added to the above treatments and titrated up to 12.5 mg twice a day and continued for at least 6 months.

The Clinician Erythema Assessment 5-point scale before therapy was 3.4 and dropped to 0.4 during therapy, while the patient self-assessment before therapy was 3.8 and dropped to 0.8 during therapy.

Another study evaluated the use of propranolol and/or doxycycline in 78 patients with rosacea. The propranolol and combination treatment groups showed more rapid improvement at weeks 4 and 8, but there was no statistically significant difference between them by week 12. Rosacea clinical scores also decreased in all groups, but there were no significant differences between them. Reduction of Assessment of Rosacea Clinical Score was 51%, 52.2%, and 57.3% in the propranolol, doxycycline, and combination groups, respectively.

Harper disclosed ties with Almirall, Cutera, Galderma, Journey, Ortho Dermatologics, and Sun Pharmaceutical Industries.

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at least one biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to results from a phase 3 trial.

Of the 242 patients in the RESET-RA study, all received the VNS device implant but were blinded as to whether the device was turned on. At 12 weeks, 35.2% of patients receiving daily stimulation achieved 20% improvement in American College of Rheumatology response criteria (ACR20) compared with 24.2% of those with an inactive device. The response was more pronounced among patients with exposure to only one prior b/tsDMARD. A greater proportion of patients in the overall treatment group also reached low disease activity or remission compared with those who did not receive stimulation. 

The research was presented as a late-breaking poster at the ACR 2024 Annual Meeting.

“This is a particularly tough-to-treat patient population, since the patients enrolled were considered refractory to biologic therapy,” said Elena Schiopu, MD, professor of medicine in the Division of Rheumatology and director of clinical trials at the Medical College of Georgia at Augusta University. More than one third of patients in the study had tried three or more b/tsDMARDs prior to the study. “I’m pretty excited about these results,” she added. Schiopu was a RESET-RA institutional principal investigator and enrolled two patients in the trial.

These positive results are a first for VNS treatment in rheumatic diseases. Previous studies demonstrating the potential therapeutic effect of this implant approach have largely been open-label, proof-of-concept, or pilot studies. Noninvasive, wearable stimulation devices have also shown promise in open-label studies; however, a sham-controlled trial published in 2023 showed that transcutaneous vagus nerve stimulation on the ear was no more effective than placebo. 

 

But How Does It Work?

The device, developed by SetPoint Medical in Valencia, California, is about the size of a multivitamin and implanted in an outpatient setting. During the 45-minute procedure, surgeons isolate the vagus nerve on the left side of the neck and place the nerve stimulator with a silicone positioning pod to hold it in place.

The device is programmed to deliver stimulation for 1 minute every day and needs charging for only 10 minutes once a week, which is done remotely with a necklace.

The device takes advantage of the vagus nerve’s anti-inflammatory properties, stimulating the nerve to help regulate an overactive immune system of someone with RA, explained David Chernoff, MD, Setpoint Medical’s chief medical officer. 

“We’re recapitulating what nature has developed over millions of years, which is the nexus between the brain and the immune system, which happens to be mediated by the vagus nerve,” he told Medscape Medical News. 

This novel VNS approach also does not have the same immunosuppressive safety concerns as drugs commonly used to treat RA, he said. 

“We’re able to adjust the amount of inflammation, but we don’t cause the host defense issues” that are present with some of these drugs, he continued.

SetPoint Medical’s pilot study of the device in 14 patients showed promising results. Five of 10 patients randomly assigned to active VNS over 12 weeks showed clinical improvements, measured by 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index. In the remaining four patients who received sham stimulation — where the device was implanted but not activated — there were no clinical disease improvements.

 

RESET-RA Details

The most recent, much larger phase 3 study enrolled patients from 41 sites in the United States. Patients were on average 56 years old and had a body mass index of 30; 86% were women. A total of 39% had previously tried one b/tsDMARD, 22% had tried two, and 39% had tried three or more. Patients, on average, had 15 tender joints and 10 swollen joints. Patients discontinued their prior b/tsDMARD before the procedure and remained on conventional DMARDS during the trial, including methotrexate, hydroxychloroquine, and sulfasalazine.

The researchers randomly assigned patients 1:1 to active (treatment) or nonactive (control) stimulation. 

“The perception of stimulation varies from patient to patient, which itself is helpful in blinding as there is no expected perception of whether or how stimulation will be felt,” Chernoff explained. The 1-minute stimulation was scheduled in the early hours of the morning, when a patient typically would be asleep, he said.

Patients were excluded from the analysis if they were rescued by steroids or b/tsDMARDs through week 12. After week 12, the control group was switched to stimulation and efficacy was reassessed at week 24.

 

Higher ACR20 Response Rate, Lower Disease Activity

Beyond meeting the primary endpoint of ACR20 response, patients on the active stimulation group showed lower disease activity at week 12. Compared with 15.8% of patients in the control group, 27% of those in the treatment group achieved a DAS28-CRP ≤ 3.2. 

The active stimulation was particularly effective in patients who had experience with only one prior b/tsDMARD. In this subset of patients, 44.2% in the treatment group achieved ACR20 compared with 19.0% in the control group.

During this sham-controlled trial period, 13.1% of patients in the treatment group and 18.3% of patients in the control group reported an adverse event (AE) related to the procedure or device, most commonly vocal cord paresis or dysphonia. In the treatment group, 8.2% reported stimulation-related AEs, most commonly mild/moderate pain that was managed by adjusting the stimulation level. 

Serious adverse events (SAEs) were relatively rare, with four treatment-related SAEs across both study groups. No AEs led to study discontinuation through week 24.

The 12-week results mirror those of the initial Humira and Enbrel trials in the late 1990s and early 2000s, Schiopu said, although in those trials, the patients were naive to biologics, and some were naive to methotrexate. A more appropriate comparison, she said, would be biologic-experienced populations.

At week 24, the percentage of patients achieving ACR20 further increased to 51.5% in the treatment group and to 53.1% in the previous control group who were now crossed over to active stimulation. In this secondary period, patients could add any additional therapies like steroids or b/tsDMARDs. At 24 weeks, 81% of patients remained on stimulation without needing additional medication, beyond their continued background DMARDs. 

The results also show “a continuum of improvement over time,” Schiopu said, where response rates climbed through week 24. 

Schiopu is particularly excited about the potential to use this stimulation device in older patients, who have perhaps been on immunosuppressant drugs for decades. 

“Aside from being chronically immunosuppressed, their immune system is more tired [due to age],” she said. With VNS therapies like SetPoint’s, “we could offer [these patients] a lesser immunosuppressive alternative that is still immune-modular enough to manage their RA.”

Schiopu is a consultant for Johnson & Johnson and reported receiving research funding for serving as an institutional principal investigator for SetPoint, Galapagos, Johnson & Johnson, Boehringer Ingelheim, Lilly, argenx, EMD Serono, Priovant, Novartis, Bristol Myers Squibb, Zena Pharmaceuticals, and Horizon/Amgen.

 

A version of this article appeared on Medscape.com.

WASHINGTON — An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at least one biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to results from a phase 3 trial.

Of the 242 patients in the RESET-RA study, all received the VNS device implant but were blinded as to whether the device was turned on. At 12 weeks, 35.2% of patients receiving daily stimulation achieved 20% improvement in American College of Rheumatology response criteria (ACR20) compared with 24.2% of those with an inactive device. The response was more pronounced among patients with exposure to only one prior b/tsDMARD. A greater proportion of patients in the overall treatment group also reached low disease activity or remission compared with those who did not receive stimulation. 

The research was presented as a late-breaking poster at the ACR 2024 Annual Meeting.

“This is a particularly tough-to-treat patient population, since the patients enrolled were considered refractory to biologic therapy,” said Elena Schiopu, MD, professor of medicine in the Division of Rheumatology and director of clinical trials at the Medical College of Georgia at Augusta University. More than one third of patients in the study had tried three or more b/tsDMARDs prior to the study. “I’m pretty excited about these results,” she added. Schiopu was a RESET-RA institutional principal investigator and enrolled two patients in the trial.

These positive results are a first for VNS treatment in rheumatic diseases. Previous studies demonstrating the potential therapeutic effect of this implant approach have largely been open-label, proof-of-concept, or pilot studies. Noninvasive, wearable stimulation devices have also shown promise in open-label studies; however, a sham-controlled trial published in 2023 showed that transcutaneous vagus nerve stimulation on the ear was no more effective than placebo. 

 

But How Does It Work?

The device, developed by SetPoint Medical in Valencia, California, is about the size of a multivitamin and implanted in an outpatient setting. During the 45-minute procedure, surgeons isolate the vagus nerve on the left side of the neck and place the nerve stimulator with a silicone positioning pod to hold it in place.

The device is programmed to deliver stimulation for 1 minute every day and needs charging for only 10 minutes once a week, which is done remotely with a necklace.

The device takes advantage of the vagus nerve’s anti-inflammatory properties, stimulating the nerve to help regulate an overactive immune system of someone with RA, explained David Chernoff, MD, Setpoint Medical’s chief medical officer. 

“We’re recapitulating what nature has developed over millions of years, which is the nexus between the brain and the immune system, which happens to be mediated by the vagus nerve,” he told Medscape Medical News. 

This novel VNS approach also does not have the same immunosuppressive safety concerns as drugs commonly used to treat RA, he said. 

“We’re able to adjust the amount of inflammation, but we don’t cause the host defense issues” that are present with some of these drugs, he continued.

SetPoint Medical’s pilot study of the device in 14 patients showed promising results. Five of 10 patients randomly assigned to active VNS over 12 weeks showed clinical improvements, measured by 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index. In the remaining four patients who received sham stimulation — where the device was implanted but not activated — there were no clinical disease improvements.

 

RESET-RA Details

The most recent, much larger phase 3 study enrolled patients from 41 sites in the United States. Patients were on average 56 years old and had a body mass index of 30; 86% were women. A total of 39% had previously tried one b/tsDMARD, 22% had tried two, and 39% had tried three or more. Patients, on average, had 15 tender joints and 10 swollen joints. Patients discontinued their prior b/tsDMARD before the procedure and remained on conventional DMARDS during the trial, including methotrexate, hydroxychloroquine, and sulfasalazine.

The researchers randomly assigned patients 1:1 to active (treatment) or nonactive (control) stimulation. 

“The perception of stimulation varies from patient to patient, which itself is helpful in blinding as there is no expected perception of whether or how stimulation will be felt,” Chernoff explained. The 1-minute stimulation was scheduled in the early hours of the morning, when a patient typically would be asleep, he said.

Patients were excluded from the analysis if they were rescued by steroids or b/tsDMARDs through week 12. After week 12, the control group was switched to stimulation and efficacy was reassessed at week 24.

 

Higher ACR20 Response Rate, Lower Disease Activity

Beyond meeting the primary endpoint of ACR20 response, patients on the active stimulation group showed lower disease activity at week 12. Compared with 15.8% of patients in the control group, 27% of those in the treatment group achieved a DAS28-CRP ≤ 3.2. 

The active stimulation was particularly effective in patients who had experience with only one prior b/tsDMARD. In this subset of patients, 44.2% in the treatment group achieved ACR20 compared with 19.0% in the control group.

During this sham-controlled trial period, 13.1% of patients in the treatment group and 18.3% of patients in the control group reported an adverse event (AE) related to the procedure or device, most commonly vocal cord paresis or dysphonia. In the treatment group, 8.2% reported stimulation-related AEs, most commonly mild/moderate pain that was managed by adjusting the stimulation level. 

Serious adverse events (SAEs) were relatively rare, with four treatment-related SAEs across both study groups. No AEs led to study discontinuation through week 24.

The 12-week results mirror those of the initial Humira and Enbrel trials in the late 1990s and early 2000s, Schiopu said, although in those trials, the patients were naive to biologics, and some were naive to methotrexate. A more appropriate comparison, she said, would be biologic-experienced populations.

At week 24, the percentage of patients achieving ACR20 further increased to 51.5% in the treatment group and to 53.1% in the previous control group who were now crossed over to active stimulation. In this secondary period, patients could add any additional therapies like steroids or b/tsDMARDs. At 24 weeks, 81% of patients remained on stimulation without needing additional medication, beyond their continued background DMARDs. 

The results also show “a continuum of improvement over time,” Schiopu said, where response rates climbed through week 24. 

Schiopu is particularly excited about the potential to use this stimulation device in older patients, who have perhaps been on immunosuppressant drugs for decades. 

“Aside from being chronically immunosuppressed, their immune system is more tired [due to age],” she said. With VNS therapies like SetPoint’s, “we could offer [these patients] a lesser immunosuppressive alternative that is still immune-modular enough to manage their RA.”

Schiopu is a consultant for Johnson & Johnson and reported receiving research funding for serving as an institutional principal investigator for SetPoint, Galapagos, Johnson & Johnson, Boehringer Ingelheim, Lilly, argenx, EMD Serono, Priovant, Novartis, Bristol Myers Squibb, Zena Pharmaceuticals, and Horizon/Amgen.

 

A version of this article appeared on Medscape.com.

WASHINGTON — An implantable vagus nerve stimulation (VNS) device effectively treats moderate to severe rheumatoid arthritis (RA) in patients who had previously failed at least one biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), according to results from a phase 3 trial.

Of the 242 patients in the RESET-RA study, all received the VNS device implant but were blinded as to whether the device was turned on. At 12 weeks, 35.2% of patients receiving daily stimulation achieved 20% improvement in American College of Rheumatology response criteria (ACR20) compared with 24.2% of those with an inactive device. The response was more pronounced among patients with exposure to only one prior b/tsDMARD. A greater proportion of patients in the overall treatment group also reached low disease activity or remission compared with those who did not receive stimulation. 

The research was presented as a late-breaking poster at the ACR 2024 Annual Meeting.

“This is a particularly tough-to-treat patient population, since the patients enrolled were considered refractory to biologic therapy,” said Elena Schiopu, MD, professor of medicine in the Division of Rheumatology and director of clinical trials at the Medical College of Georgia at Augusta University. More than one third of patients in the study had tried three or more b/tsDMARDs prior to the study. “I’m pretty excited about these results,” she added. Schiopu was a RESET-RA institutional principal investigator and enrolled two patients in the trial.

These positive results are a first for VNS treatment in rheumatic diseases. Previous studies demonstrating the potential therapeutic effect of this implant approach have largely been open-label, proof-of-concept, or pilot studies. Noninvasive, wearable stimulation devices have also shown promise in open-label studies; however, a sham-controlled trial published in 2023 showed that transcutaneous vagus nerve stimulation on the ear was no more effective than placebo. 

 

But How Does It Work?

The device, developed by SetPoint Medical in Valencia, California, is about the size of a multivitamin and implanted in an outpatient setting. During the 45-minute procedure, surgeons isolate the vagus nerve on the left side of the neck and place the nerve stimulator with a silicone positioning pod to hold it in place.

The device is programmed to deliver stimulation for 1 minute every day and needs charging for only 10 minutes once a week, which is done remotely with a necklace.

The device takes advantage of the vagus nerve’s anti-inflammatory properties, stimulating the nerve to help regulate an overactive immune system of someone with RA, explained David Chernoff, MD, Setpoint Medical’s chief medical officer. 

“We’re recapitulating what nature has developed over millions of years, which is the nexus between the brain and the immune system, which happens to be mediated by the vagus nerve,” he told Medscape Medical News. 

This novel VNS approach also does not have the same immunosuppressive safety concerns as drugs commonly used to treat RA, he said. 

“We’re able to adjust the amount of inflammation, but we don’t cause the host defense issues” that are present with some of these drugs, he continued.

SetPoint Medical’s pilot study of the device in 14 patients showed promising results. Five of 10 patients randomly assigned to active VNS over 12 weeks showed clinical improvements, measured by 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index. In the remaining four patients who received sham stimulation — where the device was implanted but not activated — there were no clinical disease improvements.

 

RESET-RA Details

The most recent, much larger phase 3 study enrolled patients from 41 sites in the United States. Patients were on average 56 years old and had a body mass index of 30; 86% were women. A total of 39% had previously tried one b/tsDMARD, 22% had tried two, and 39% had tried three or more. Patients, on average, had 15 tender joints and 10 swollen joints. Patients discontinued their prior b/tsDMARD before the procedure and remained on conventional DMARDS during the trial, including methotrexate, hydroxychloroquine, and sulfasalazine.

The researchers randomly assigned patients 1:1 to active (treatment) or nonactive (control) stimulation. 

“The perception of stimulation varies from patient to patient, which itself is helpful in blinding as there is no expected perception of whether or how stimulation will be felt,” Chernoff explained. The 1-minute stimulation was scheduled in the early hours of the morning, when a patient typically would be asleep, he said.

Patients were excluded from the analysis if they were rescued by steroids or b/tsDMARDs through week 12. After week 12, the control group was switched to stimulation and efficacy was reassessed at week 24.

 

Higher ACR20 Response Rate, Lower Disease Activity

Beyond meeting the primary endpoint of ACR20 response, patients on the active stimulation group showed lower disease activity at week 12. Compared with 15.8% of patients in the control group, 27% of those in the treatment group achieved a DAS28-CRP ≤ 3.2. 

The active stimulation was particularly effective in patients who had experience with only one prior b/tsDMARD. In this subset of patients, 44.2% in the treatment group achieved ACR20 compared with 19.0% in the control group.

During this sham-controlled trial period, 13.1% of patients in the treatment group and 18.3% of patients in the control group reported an adverse event (AE) related to the procedure or device, most commonly vocal cord paresis or dysphonia. In the treatment group, 8.2% reported stimulation-related AEs, most commonly mild/moderate pain that was managed by adjusting the stimulation level. 

Serious adverse events (SAEs) were relatively rare, with four treatment-related SAEs across both study groups. No AEs led to study discontinuation through week 24.

The 12-week results mirror those of the initial Humira and Enbrel trials in the late 1990s and early 2000s, Schiopu said, although in those trials, the patients were naive to biologics, and some were naive to methotrexate. A more appropriate comparison, she said, would be biologic-experienced populations.

At week 24, the percentage of patients achieving ACR20 further increased to 51.5% in the treatment group and to 53.1% in the previous control group who were now crossed over to active stimulation. In this secondary period, patients could add any additional therapies like steroids or b/tsDMARDs. At 24 weeks, 81% of patients remained on stimulation without needing additional medication, beyond their continued background DMARDs. 

The results also show “a continuum of improvement over time,” Schiopu said, where response rates climbed through week 24. 

Schiopu is particularly excited about the potential to use this stimulation device in older patients, who have perhaps been on immunosuppressant drugs for decades. 

“Aside from being chronically immunosuppressed, their immune system is more tired [due to age],” she said. With VNS therapies like SetPoint’s, “we could offer [these patients] a lesser immunosuppressive alternative that is still immune-modular enough to manage their RA.”

Schiopu is a consultant for Johnson & Johnson and reported receiving research funding for serving as an institutional principal investigator for SetPoint, Galapagos, Johnson & Johnson, Boehringer Ingelheim, Lilly, argenx, EMD Serono, Priovant, Novartis, Bristol Myers Squibb, Zena Pharmaceuticals, and Horizon/Amgen.

 

A version of this article appeared on Medscape.com.