More than 1.2 million Americans are living with HIV, and more than 30,000 new cases are diagnosed each year. While total incidence has declined since 2016, HIV remains a nationwide epidemic.¹

Medications that prevent HIV acquisition, termed preexposure prophylaxis (PrEP), are an important tool to initiate in the primary care setting to reduce HIV transmission. However, while there are an estimated 1.2 million people eligible for PrEP, only 36% have received PrEP prescriptions.² Several barriers that have impeded its widespread adoption include a lack of clinician knowledge and clinical resources for testing, high medication costs, and stigma around sexual health and intravenous (IV) drug use.

The value of PrEP

PrEP is chemoprophylaxis against the acquisition of HIV infection through the administration of an oral or injectable medication to people at risk for HIV. This practice began in the early 2000s, with the first oral regimen approved in 2012, and since has become an important tool in preventing HIV transmission.

When taken as prescribed, PrEP medications reduce the risk for acquiring HIV through sex by approximately 99% and can reduce the risk for acquiring HIV from injection drug use by approximately 74%.³ The US Preventive Services Task Force issued a Grade “A” recommendation to offer PrEP to people at high risk for HIV acquisition in June 2019 and reaffirmed it in a 2023 update.⁴

PrEP is notably distinct from postexposure prophylaxis (PEP), which is the administration of medication to prevent HIV infection after a possible exposure.

The available regimens

Regimens for PrEP include oral tablets or intramuscular (IM) injections.⁵ There are 3 PrEP regimens approved by the US Food and Drug Administration (FDA): tenofovir disoproxil fumarate/­emtricitabine (Truvada), tenofovir ­alafenamide/emtricitabine (Descovy), and cabotegravir (Apretude).

Incomplete adherence to or abrupt discontinuation of oral PrEP could precipitate a hepatitis B flare.

Truvada is once-daily oral PrEP that was approved in 2012 and is now available in a generic formulation. Notable adverse effects of Truvada include a small negative impact on renal function and small reductions in bone mineral density; these have been noted in individual trials, but in meta-­analyses such differences were not found to be statistically significant.^6-8 The most common adverse effects of Truvada, experienced by up to 6% of patients, are gastrointestinal symptoms, fatigue, headache/dizziness, depression, and insomnia; most symptoms resolve within weeks.

Continue to: Descovy

Descovy is daily oral PrEP that was approved in 2019. Descovy is associated with increases in LDL and triglycerides but has less impact on renal and bone health.⁹ The most common adverse effect of Descovy, experienced by about 5% of patients, is diarrhea, followed by nausea.

Apretude was approved in 2021 and is a 600-mg IM injection given monthly for 2 months, then every 2 months (± 7 days). The advantages of Apretude are frequency and discreteness of dosing and the ability to use in patients with estimated creatinine clearance (eCrCl) > 15 mL/min. The most common adverse effects of Apretude are injection-site reactions, which occur in 30% to 80% of patients but are rarely significant enough to lead to discontinuation (< 2% of patients discontinue use due to injection-site reactions).¹⁰ 

Who should take PrEP?

The latest Centers for Disease Control and Prevention (CDC) guidelines recommend that all sexually active adults receive information about PrEP.⁵ Indications for PrEP are broad and summarized in the FIGURE.⁵

PrEP is indicated in patients who report sexual or injection drug use behaviors that place them at substantial ongoing risk for HIV exposure. Specific indications include patients with sexual partner(s) with unknown HIV status with whom they have inconsistent or no condom use, a history of bacterial sexually transmitted infection (STI) in the past 6 months, an HIV-positive sexual partner, or the sharing of injection drug equipment.

Hepatitis B infection is not a contraindication for PrEP use, but knowledge of infection status is essential. All current oral medications used for PrEP have activity against hepatitis B. Incomplete adherence to or abrupt discontinuation of oral PrEP could precipitate a hepatitis B flare. Hepatitis B surface antigen should be tested at the time of PrEP initiation, although PrEP can begin while testing is in process.

Continue to: How to use PrEP

 

 

How to use PrEP

At PrEP initiation, acute or chronic HIV infection must be excluded with a documented negative HIV antigen/antibody test within 1 week of prescribing PrEP.⁵ The CDC guidelines provide an updated HIV testing algorithm (www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf, p 30-31, Figures 4a and 4b), which considers whether patients have received PrEP recently.

Patients with recent high-risk exposures or symptoms of acute HIV at the time of desired PrEP initiation should have an HIV-1 viral load checked with negative results before PrEP is prescribed. Additional criteria for PrEP include weight > 35 kg; screening for hepatitis B virus infection; screening for drug interactions; and drug-specific eCrCl cutoffs of > 60 mL/min for Truvada, > 30 mL/min for Descovy, and > 15 mL/min for Apretude.⁵

Studies regarding time to medication effectiveness are limited. Pharmacokinetic studies of Truvada demonstrate sufficient drug concentrations should be present in peripheral blood mononuclear cells and rectal tissue within 7 days of initiation of oral dosing and around 20 days in vaginal tissue.

Of note, while expedited partner therapy is used as a harm-reduction strategy to treat the sexual partners of patients diagnosed with certain STIs, PrEP is not recommended to be used in this way.

Ongoing monitoring with PrEP. Once oral PrEP is started, STI risk assessment and HIV testing via 4th generation antibody/antigen­ test should be completed at least every 3 months. PrEP oral prescription refills should be limited to 3 months. For patients receiving IM PrEP (Apretude), HIV testing via viral load and antibody/antigen testing should be done at the time of each injection (every 2 months).⁵

Continue to: With oral PrEP...

With oral PrEP, renal function should be checked every 6 months in patients older than 50 years or those with eCrCl < 90 mL/min at initiation. For patients younger than 50 years with no baseline renal dysfunction, the latest guidelines now recommend monitoring every 12 months instead of 6 months.⁵

For patients on Descovy, a lipid panel is recommended at PrEP initiation and every 12 months. Testing for other STIs can be considered on this schedule, based on clinical assessment. The TABLE⁵ summarizes recommended monitoring for patients taking oral PrEP.

Recommended follow-up provides an opportunity to have frequent contact with a potentially high-risk population, and PrEP should be one part of a comprehensive HIV prevention and risk reduction plan. Many patients at high risk for HIV acquisition may benefit from frequent follow-up to address screening, referral, and treatment of substance use disorders, mental health conditions, and chronic medical conditions (including hepatitis C infection) and provide ongoing preventive health care. 

Special uses of PrEP 

Same-day PrEP. Starting PrEP on the day of the initial appointment may be appropriate based on patient risk factors and barriers to care, such as a high risk for contracting HIV before the subsequent appointment for a prescription of PrEP or an inability to return to the clinic in a timely fashion due to transportation or work constraints, or clinician availability. For these patients, assuming there is a low concern for acute or chronic HIV infection, PrEP can be initiated on the day of the initial visit.⁵

In these cases, point-of-care HIV and creatinine testing with same-day results should be completed. Antigen/antibody fingerstick testing or HIV-1 RNA test are preferred; oral fluid HIV testing should not be used for same-day PrEP due to its lower sensitivity for HIV detection. If same-day testing is unavailable, blood should be drawn at the visit so that HIV and creatinine testing can be completed as soon as possible.

Continue to: In addition to initial laboratory testing...

In addition to initial laboratory testing, clinics offering same-day PrEP should be able to provide: (1) assistance for patients to enroll in health insurance or a medication assistance program (eg, Ready, Set, PrEP) for those ineligible for insurance coverage, (2) rapid follow-­up on all laboratory results with reliable patient contact information, and (3) follow-up appointments with clinicians able to prescribe and administer PrEP medications.

Off-label “on-demand” PrEP. An off-label treatment regimen for men who have sex with men (MSM) is termed “on-demand” PrEP or “2-1-1 PrEP” and is included in the CDC guidelines for consideration by clinicians.⁵ This alternative dosing schedule can be used for individuals who have sex less frequently and in a more planned fashion.

On-demand PrEP requires a patient to take 2 tablets of Truvada 2 to 24 hours before sex, followed by 1 tablet 24 hours and 1 tablet 48 hours after sexual activity. If a sexual act occurs at 48 hours, the patient should extend the daily dose for 48 additional hours, such that PrEP is always used daily for 48 hours after the last sex act.

This method has been studied with Truvada in MSM in Europe and Canada through the IPERGAY and PREVENIR trials and shown to have ≥ 86% efficacy in preventing HIV acquisition.^11,12 The only US-based study showed lower efficacy; however, based on the currently available data, the International Antiviral Society-USA Panel has recommended it as an alternative regimen.^13,14

PrEP via telehealth. Visits for PrEP initiation and continuation can be completed via telehealth.⁵ Patients then can complete necessary laboratory tests by going to a physical laboratory location or using mailed specimen kits in which they can self-collect urine, oral/rectal swabs, and fingerstick blood samples.

Continue to: PrEP use in specific populations

 

 

PrEP use in specific populations

Adolescents

Truvada, Descovy, and Apretude all are now approved for use in adolescents weighing ≥ 35 kg. Two important considerations when prescribing to this population are the effects of Truvada on bone health and the unique barriers to access.

In studies of adolescent MSM using Truvada for PrEP, bone mineral density declined, especially among those ages 15 to 19 years.¹⁵ As such, the clinical impact of decreased bone mineral density should be weighed against the risk for HIV acquisition; however, bone mineral density monitoring is not recommended in the current guidelines. CDC guidelines suggest considering Descovy for male adolescents given its potential lower impact on bone mineral density.⁵

Confidentiality and legal issues exist when prescribing PrEP to minors. In terms of parental/guardian involvement, clinicians who are prescribing PrEP for patients younger than 18 years should consult the CDC website for guidance on local and state regulations that govern prescribing and confidentiality (www.cdc.gov/hiv/policies/law/states/­minors.html).

CDC guidelines suggest considering Descovy for male adolescents given its potential lower impact on bone mineral density.

Insurance billing statements may lead to inadvertent disclosure of a minor’s decision to take PrEP to their legal guardian.¹⁶ Generic Truvada costs less than $100 for a 3-month supply when using goodrx.com, which may offer an alternative to insurance for medication payment. 

Peripartum patients

The increased risk for HIV acquisition in the peripartum period for female patients is well documented.¹⁷ Guidelines recommend offering PrEP with Truvada to female patients at risk for conception, currently pregnant, or breastfeeding when that patient’s partner has HIV and the partner’s viral load is unknown or detectable. Descovy is not recommended for pregnant or breastfeeding patients.⁵ Cabotegravir­-containing regimens (Apretude) have not been approved by the FDA for pregnant or breastfeeding patients.⁵

Continue to: Data on the impact of...

Data on the impact of Truvada for PrEP on fetal health are still emerging. A large study in Kenya showed no significant differences in preterm birth, low birth weight, or early infant growth, and a randomized, noninferiority trial in South Africa showed no association between Truvada for PrEP and preterm birth or the birth of small-for-­gestational-age infants.^18,19 There are no definitive studies of breastfeeding infants exposed to Truvada, but data from previous trials of breastfeeding mothers who were taking the individual components that are combined in the Truvada pill indicated there is minimal medication exposure to the infant.⁵

PrEP studies in the peripartum period to date have been conducted exclusively among cisgender women, and data do not yet reflect the experiences of transgender men, genderqueer people, and nonbinary individuals in the peripartum period.⁵

Transgender people

Transgender women should be strongly considered candidates for PrEP as they are at an extremely high risk for HIV acquisition. The most recent National HIV Behavioral Surveillance survey found that approximately 42% of transgender women were living with HIV.²⁰ The survey revealed stark racial and ethnic disparities among transgender women living with HIV: 62% identified as Black/African American, compared with 35% Hispanic/Latina and 17% White.²⁰

Transgender women report high rates of sexual assault, unprotected receptive anal sex, commercial sex work, homelessness, mental health disorders, and substance use, putting them at increased risk for HIV acquisition.²¹ However, transgender women are less likely to have discussed PrEP with a clinician, are less likely to be on PrEP even when interested in starting, and have higher rates of medication nonadherence compared with cisgender MSM.^21,22 PrEP has not been found to decrease levels of feminizing hormones; however, studies are mixed as to whether feminizing hormones decrease Truvada concentrations in rectal mucosa, so clinicians should emphasize the importance of daily medication adherence.²³

Transgender men have not been included in any PrEP trials, so no specific recommendations are available. 

Continue to: Disparities in PrEP access and use exist

 

 

Disparities in PrEP access and use exist

The lifetime risk for HIV acquisition is 9% among White MSM, 50% among Black MSM, and 20% among Hispanic MSM.²⁴ Despite this large disparity in disease burden, Black and Hispanic individuals are less likely to be aware of PrEP, have discussed PrEP with a health care professional, or used PrEP compared with their White counterparts.²⁵ As a result, in 2020, PrEP coverage for eligible White individuals was 61%, while coverage among eligible Black and Hispanic/Latino individuals was just 8% and 14%, respectively.²⁶

Rural areas have been shown to lag behind urban areas in PrEP awareness and use.

Surveillance data comparing male and female PrEP coverage reveal further disparities between the sexes, with PrEP coverage for eligible female-at-birth patients estimated to be 9% compared with 25.8% for male-at-birth patients.²⁶ The gap between the risk for HIV infection and the access to and uptake of PrEP coverage is most pronounced among Black women, for whom the rate of new HIV diagnosis is > 10 times higher than it is for White women, but who have some of the lowest awareness and utilization rates of all demographics.²⁷

The rural population at risk. Disparities in HIV awareness and PrEP use also exist between rural and urban populations, as well as by health insurance status. Rural areas have been shown to lag behind urban areas in PrEP awareness and use. Two potential explanations for this disparity are differences­ in HIV- and drug use–associated stigma and health insurance status. Greater stigma against drug use and HIV in rural areas has been associated with lower rates of PrEP use.²⁸

Individuals younger than 65 years in rural areas are less likely to have private health insurance and more likely to be uninsured compared with their urban counterparts, which may impact access to clinicians knowledgeable about PrEP.²⁹ Notably, MSM who live in states that have expanded Medicaid have higher rates of PrEP use compared with MSM living in states that have not expanded Medicaid.³⁰

Health insurers in the United States are required to cover PrEP medication, clinician visits, and associated blood work with no patient cost-sharing, although implementation barriers such as prior authorizations still exist. 

Conclusion

Family physicians are well positioned to identify patients at risk for HIV infection, prescribe PrEP, organize comprehensive follow-up care, and partner with their health systems and local communities to reduce barriers to care. Those who can leverage existing relationships with local health departments, school-based health clinics, congregate housing programs, LGBTQIA+ advocacy groups, harm-reduction coalitions, and other community-based organizations to raise PrEP awareness play a critical role in preventing HIV transmission and reducing health care disparities in their communities.

CORRESPONDENCE
Andrew V.A. Foley, MD, MPH, Erie Family Health Centers, 2418 W Division Street, Chicago, IL 60622; [email protected]

More than 1.2 million Americans are living with HIV, and more than 30,000 new cases are diagnosed each year. While total incidence has declined since 2016, HIV remains a nationwide epidemic.¹

Medications that prevent HIV acquisition, termed preexposure prophylaxis (PrEP), are an important tool to initiate in the primary care setting to reduce HIV transmission. However, while there are an estimated 1.2 million people eligible for PrEP, only 36% have received PrEP prescriptions.² Several barriers that have impeded its widespread adoption include a lack of clinician knowledge and clinical resources for testing, high medication costs, and stigma around sexual health and intravenous (IV) drug use.

The value of PrEP

PrEP is chemoprophylaxis against the acquisition of HIV infection through the administration of an oral or injectable medication to people at risk for HIV. This practice began in the early 2000s, with the first oral regimen approved in 2012, and since has become an important tool in preventing HIV transmission.

When taken as prescribed, PrEP medications reduce the risk for acquiring HIV through sex by approximately 99% and can reduce the risk for acquiring HIV from injection drug use by approximately 74%.³ The US Preventive Services Task Force issued a Grade “A” recommendation to offer PrEP to people at high risk for HIV acquisition in June 2019 and reaffirmed it in a 2023 update.⁴

PrEP is notably distinct from postexposure prophylaxis (PEP), which is the administration of medication to prevent HIV infection after a possible exposure.

The available regimens

Regimens for PrEP include oral tablets or intramuscular (IM) injections.⁵ There are 3 PrEP regimens approved by the US Food and Drug Administration (FDA): tenofovir disoproxil fumarate/­emtricitabine (Truvada), tenofovir ­alafenamide/emtricitabine (Descovy), and cabotegravir (Apretude).

Incomplete adherence to or abrupt discontinuation of oral PrEP could precipitate a hepatitis B flare.

Truvada is once-daily oral PrEP that was approved in 2012 and is now available in a generic formulation. Notable adverse effects of Truvada include a small negative impact on renal function and small reductions in bone mineral density; these have been noted in individual trials, but in meta-­analyses such differences were not found to be statistically significant.^6-8 The most common adverse effects of Truvada, experienced by up to 6% of patients, are gastrointestinal symptoms, fatigue, headache/dizziness, depression, and insomnia; most symptoms resolve within weeks.

Continue to: Descovy

Descovy is daily oral PrEP that was approved in 2019. Descovy is associated with increases in LDL and triglycerides but has less impact on renal and bone health.⁹ The most common adverse effect of Descovy, experienced by about 5% of patients, is diarrhea, followed by nausea.

Apretude was approved in 2021 and is a 600-mg IM injection given monthly for 2 months, then every 2 months (± 7 days). The advantages of Apretude are frequency and discreteness of dosing and the ability to use in patients with estimated creatinine clearance (eCrCl) > 15 mL/min. The most common adverse effects of Apretude are injection-site reactions, which occur in 30% to 80% of patients but are rarely significant enough to lead to discontinuation (< 2% of patients discontinue use due to injection-site reactions).¹⁰ 

Who should take PrEP?

The latest Centers for Disease Control and Prevention (CDC) guidelines recommend that all sexually active adults receive information about PrEP.⁵ Indications for PrEP are broad and summarized in the FIGURE.⁵

PrEP is indicated in patients who report sexual or injection drug use behaviors that place them at substantial ongoing risk for HIV exposure. Specific indications include patients with sexual partner(s) with unknown HIV status with whom they have inconsistent or no condom use, a history of bacterial sexually transmitted infection (STI) in the past 6 months, an HIV-positive sexual partner, or the sharing of injection drug equipment.

Hepatitis B infection is not a contraindication for PrEP use, but knowledge of infection status is essential. All current oral medications used for PrEP have activity against hepatitis B. Incomplete adherence to or abrupt discontinuation of oral PrEP could precipitate a hepatitis B flare. Hepatitis B surface antigen should be tested at the time of PrEP initiation, although PrEP can begin while testing is in process.

Continue to: How to use PrEP

 

 

How to use PrEP

At PrEP initiation, acute or chronic HIV infection must be excluded with a documented negative HIV antigen/antibody test within 1 week of prescribing PrEP.⁵ The CDC guidelines provide an updated HIV testing algorithm (www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf, p 30-31, Figures 4a and 4b), which considers whether patients have received PrEP recently.

Patients with recent high-risk exposures or symptoms of acute HIV at the time of desired PrEP initiation should have an HIV-1 viral load checked with negative results before PrEP is prescribed. Additional criteria for PrEP include weight > 35 kg; screening for hepatitis B virus infection; screening for drug interactions; and drug-specific eCrCl cutoffs of > 60 mL/min for Truvada, > 30 mL/min for Descovy, and > 15 mL/min for Apretude.⁵

Studies regarding time to medication effectiveness are limited. Pharmacokinetic studies of Truvada demonstrate sufficient drug concentrations should be present in peripheral blood mononuclear cells and rectal tissue within 7 days of initiation of oral dosing and around 20 days in vaginal tissue.

Of note, while expedited partner therapy is used as a harm-reduction strategy to treat the sexual partners of patients diagnosed with certain STIs, PrEP is not recommended to be used in this way.

Ongoing monitoring with PrEP. Once oral PrEP is started, STI risk assessment and HIV testing via 4th generation antibody/antigen­ test should be completed at least every 3 months. PrEP oral prescription refills should be limited to 3 months. For patients receiving IM PrEP (Apretude), HIV testing via viral load and antibody/antigen testing should be done at the time of each injection (every 2 months).⁵

Continue to: With oral PrEP...

With oral PrEP, renal function should be checked every 6 months in patients older than 50 years or those with eCrCl < 90 mL/min at initiation. For patients younger than 50 years with no baseline renal dysfunction, the latest guidelines now recommend monitoring every 12 months instead of 6 months.⁵

For patients on Descovy, a lipid panel is recommended at PrEP initiation and every 12 months. Testing for other STIs can be considered on this schedule, based on clinical assessment. The TABLE⁵ summarizes recommended monitoring for patients taking oral PrEP.

Recommended follow-up provides an opportunity to have frequent contact with a potentially high-risk population, and PrEP should be one part of a comprehensive HIV prevention and risk reduction plan. Many patients at high risk for HIV acquisition may benefit from frequent follow-up to address screening, referral, and treatment of substance use disorders, mental health conditions, and chronic medical conditions (including hepatitis C infection) and provide ongoing preventive health care. 

Special uses of PrEP 

Same-day PrEP. Starting PrEP on the day of the initial appointment may be appropriate based on patient risk factors and barriers to care, such as a high risk for contracting HIV before the subsequent appointment for a prescription of PrEP or an inability to return to the clinic in a timely fashion due to transportation or work constraints, or clinician availability. For these patients, assuming there is a low concern for acute or chronic HIV infection, PrEP can be initiated on the day of the initial visit.⁵

In these cases, point-of-care HIV and creatinine testing with same-day results should be completed. Antigen/antibody fingerstick testing or HIV-1 RNA test are preferred; oral fluid HIV testing should not be used for same-day PrEP due to its lower sensitivity for HIV detection. If same-day testing is unavailable, blood should be drawn at the visit so that HIV and creatinine testing can be completed as soon as possible.

Continue to: In addition to initial laboratory testing...

In addition to initial laboratory testing, clinics offering same-day PrEP should be able to provide: (1) assistance for patients to enroll in health insurance or a medication assistance program (eg, Ready, Set, PrEP) for those ineligible for insurance coverage, (2) rapid follow-­up on all laboratory results with reliable patient contact information, and (3) follow-up appointments with clinicians able to prescribe and administer PrEP medications.

Off-label “on-demand” PrEP. An off-label treatment regimen for men who have sex with men (MSM) is termed “on-demand” PrEP or “2-1-1 PrEP” and is included in the CDC guidelines for consideration by clinicians.⁵ This alternative dosing schedule can be used for individuals who have sex less frequently and in a more planned fashion.

On-demand PrEP requires a patient to take 2 tablets of Truvada 2 to 24 hours before sex, followed by 1 tablet 24 hours and 1 tablet 48 hours after sexual activity. If a sexual act occurs at 48 hours, the patient should extend the daily dose for 48 additional hours, such that PrEP is always used daily for 48 hours after the last sex act.

This method has been studied with Truvada in MSM in Europe and Canada through the IPERGAY and PREVENIR trials and shown to have ≥ 86% efficacy in preventing HIV acquisition.^11,12 The only US-based study showed lower efficacy; however, based on the currently available data, the International Antiviral Society-USA Panel has recommended it as an alternative regimen.^13,14

PrEP via telehealth. Visits for PrEP initiation and continuation can be completed via telehealth.⁵ Patients then can complete necessary laboratory tests by going to a physical laboratory location or using mailed specimen kits in which they can self-collect urine, oral/rectal swabs, and fingerstick blood samples.

Continue to: PrEP use in specific populations

 

 

PrEP use in specific populations

Adolescents

Truvada, Descovy, and Apretude all are now approved for use in adolescents weighing ≥ 35 kg. Two important considerations when prescribing to this population are the effects of Truvada on bone health and the unique barriers to access.

In studies of adolescent MSM using Truvada for PrEP, bone mineral density declined, especially among those ages 15 to 19 years.¹⁵ As such, the clinical impact of decreased bone mineral density should be weighed against the risk for HIV acquisition; however, bone mineral density monitoring is not recommended in the current guidelines. CDC guidelines suggest considering Descovy for male adolescents given its potential lower impact on bone mineral density.⁵

Confidentiality and legal issues exist when prescribing PrEP to minors. In terms of parental/guardian involvement, clinicians who are prescribing PrEP for patients younger than 18 years should consult the CDC website for guidance on local and state regulations that govern prescribing and confidentiality (www.cdc.gov/hiv/policies/law/states/­minors.html).

CDC guidelines suggest considering Descovy for male adolescents given its potential lower impact on bone mineral density.

Insurance billing statements may lead to inadvertent disclosure of a minor’s decision to take PrEP to their legal guardian.¹⁶ Generic Truvada costs less than $100 for a 3-month supply when using goodrx.com, which may offer an alternative to insurance for medication payment. 

Peripartum patients

The increased risk for HIV acquisition in the peripartum period for female patients is well documented.¹⁷ Guidelines recommend offering PrEP with Truvada to female patients at risk for conception, currently pregnant, or breastfeeding when that patient’s partner has HIV and the partner’s viral load is unknown or detectable. Descovy is not recommended for pregnant or breastfeeding patients.⁵ Cabotegravir­-containing regimens (Apretude) have not been approved by the FDA for pregnant or breastfeeding patients.⁵

Continue to: Data on the impact of...

Data on the impact of Truvada for PrEP on fetal health are still emerging. A large study in Kenya showed no significant differences in preterm birth, low birth weight, or early infant growth, and a randomized, noninferiority trial in South Africa showed no association between Truvada for PrEP and preterm birth or the birth of small-for-­gestational-age infants.^18,19 There are no definitive studies of breastfeeding infants exposed to Truvada, but data from previous trials of breastfeeding mothers who were taking the individual components that are combined in the Truvada pill indicated there is minimal medication exposure to the infant.⁵

PrEP studies in the peripartum period to date have been conducted exclusively among cisgender women, and data do not yet reflect the experiences of transgender men, genderqueer people, and nonbinary individuals in the peripartum period.⁵

Transgender people

Transgender women should be strongly considered candidates for PrEP as they are at an extremely high risk for HIV acquisition. The most recent National HIV Behavioral Surveillance survey found that approximately 42% of transgender women were living with HIV.²⁰ The survey revealed stark racial and ethnic disparities among transgender women living with HIV: 62% identified as Black/African American, compared with 35% Hispanic/Latina and 17% White.²⁰

Transgender women report high rates of sexual assault, unprotected receptive anal sex, commercial sex work, homelessness, mental health disorders, and substance use, putting them at increased risk for HIV acquisition.²¹ However, transgender women are less likely to have discussed PrEP with a clinician, are less likely to be on PrEP even when interested in starting, and have higher rates of medication nonadherence compared with cisgender MSM.^21,22 PrEP has not been found to decrease levels of feminizing hormones; however, studies are mixed as to whether feminizing hormones decrease Truvada concentrations in rectal mucosa, so clinicians should emphasize the importance of daily medication adherence.²³

Transgender men have not been included in any PrEP trials, so no specific recommendations are available. 

Continue to: Disparities in PrEP access and use exist

 

 

Disparities in PrEP access and use exist

The lifetime risk for HIV acquisition is 9% among White MSM, 50% among Black MSM, and 20% among Hispanic MSM.²⁴ Despite this large disparity in disease burden, Black and Hispanic individuals are less likely to be aware of PrEP, have discussed PrEP with a health care professional, or used PrEP compared with their White counterparts.²⁵ As a result, in 2020, PrEP coverage for eligible White individuals was 61%, while coverage among eligible Black and Hispanic/Latino individuals was just 8% and 14%, respectively.²⁶

Rural areas have been shown to lag behind urban areas in PrEP awareness and use.

Surveillance data comparing male and female PrEP coverage reveal further disparities between the sexes, with PrEP coverage for eligible female-at-birth patients estimated to be 9% compared with 25.8% for male-at-birth patients.²⁶ The gap between the risk for HIV infection and the access to and uptake of PrEP coverage is most pronounced among Black women, for whom the rate of new HIV diagnosis is > 10 times higher than it is for White women, but who have some of the lowest awareness and utilization rates of all demographics.²⁷

The rural population at risk. Disparities in HIV awareness and PrEP use also exist between rural and urban populations, as well as by health insurance status. Rural areas have been shown to lag behind urban areas in PrEP awareness and use. Two potential explanations for this disparity are differences­ in HIV- and drug use–associated stigma and health insurance status. Greater stigma against drug use and HIV in rural areas has been associated with lower rates of PrEP use.²⁸

Individuals younger than 65 years in rural areas are less likely to have private health insurance and more likely to be uninsured compared with their urban counterparts, which may impact access to clinicians knowledgeable about PrEP.²⁹ Notably, MSM who live in states that have expanded Medicaid have higher rates of PrEP use compared with MSM living in states that have not expanded Medicaid.³⁰

Health insurers in the United States are required to cover PrEP medication, clinician visits, and associated blood work with no patient cost-sharing, although implementation barriers such as prior authorizations still exist. 

Conclusion

Family physicians are well positioned to identify patients at risk for HIV infection, prescribe PrEP, organize comprehensive follow-up care, and partner with their health systems and local communities to reduce barriers to care. Those who can leverage existing relationships with local health departments, school-based health clinics, congregate housing programs, LGBTQIA+ advocacy groups, harm-reduction coalitions, and other community-based organizations to raise PrEP awareness play a critical role in preventing HIV transmission and reducing health care disparities in their communities.

CORRESPONDENCE
Andrew V.A. Foley, MD, MPH, Erie Family Health Centers, 2418 W Division Street, Chicago, IL 60622; [email protected]

More than 1.2 million Americans are living with HIV, and more than 30,000 new cases are diagnosed each year. While total incidence has declined since 2016, HIV remains a nationwide epidemic.¹

Medications that prevent HIV acquisition, termed preexposure prophylaxis (PrEP), are an important tool to initiate in the primary care setting to reduce HIV transmission. However, while there are an estimated 1.2 million people eligible for PrEP, only 36% have received PrEP prescriptions.² Several barriers that have impeded its widespread adoption include a lack of clinician knowledge and clinical resources for testing, high medication costs, and stigma around sexual health and intravenous (IV) drug use.

The value of PrEP

PrEP is chemoprophylaxis against the acquisition of HIV infection through the administration of an oral or injectable medication to people at risk for HIV. This practice began in the early 2000s, with the first oral regimen approved in 2012, and since has become an important tool in preventing HIV transmission.

When taken as prescribed, PrEP medications reduce the risk for acquiring HIV through sex by approximately 99% and can reduce the risk for acquiring HIV from injection drug use by approximately 74%.³ The US Preventive Services Task Force issued a Grade “A” recommendation to offer PrEP to people at high risk for HIV acquisition in June 2019 and reaffirmed it in a 2023 update.⁴

PrEP is notably distinct from postexposure prophylaxis (PEP), which is the administration of medication to prevent HIV infection after a possible exposure.

The available regimens

Regimens for PrEP include oral tablets or intramuscular (IM) injections.⁵ There are 3 PrEP regimens approved by the US Food and Drug Administration (FDA): tenofovir disoproxil fumarate/­emtricitabine (Truvada), tenofovir ­alafenamide/emtricitabine (Descovy), and cabotegravir (Apretude).

Incomplete adherence to or abrupt discontinuation of oral PrEP could precipitate a hepatitis B flare.

Truvada is once-daily oral PrEP that was approved in 2012 and is now available in a generic formulation. Notable adverse effects of Truvada include a small negative impact on renal function and small reductions in bone mineral density; these have been noted in individual trials, but in meta-­analyses such differences were not found to be statistically significant.^6-8 The most common adverse effects of Truvada, experienced by up to 6% of patients, are gastrointestinal symptoms, fatigue, headache/dizziness, depression, and insomnia; most symptoms resolve within weeks.

Continue to: Descovy

Descovy is daily oral PrEP that was approved in 2019. Descovy is associated with increases in LDL and triglycerides but has less impact on renal and bone health.⁹ The most common adverse effect of Descovy, experienced by about 5% of patients, is diarrhea, followed by nausea.

Apretude was approved in 2021 and is a 600-mg IM injection given monthly for 2 months, then every 2 months (± 7 days). The advantages of Apretude are frequency and discreteness of dosing and the ability to use in patients with estimated creatinine clearance (eCrCl) > 15 mL/min. The most common adverse effects of Apretude are injection-site reactions, which occur in 30% to 80% of patients but are rarely significant enough to lead to discontinuation (< 2% of patients discontinue use due to injection-site reactions).¹⁰ 

Who should take PrEP?

The latest Centers for Disease Control and Prevention (CDC) guidelines recommend that all sexually active adults receive information about PrEP.⁵ Indications for PrEP are broad and summarized in the FIGURE.⁵

PrEP is indicated in patients who report sexual or injection drug use behaviors that place them at substantial ongoing risk for HIV exposure. Specific indications include patients with sexual partner(s) with unknown HIV status with whom they have inconsistent or no condom use, a history of bacterial sexually transmitted infection (STI) in the past 6 months, an HIV-positive sexual partner, or the sharing of injection drug equipment.

Hepatitis B infection is not a contraindication for PrEP use, but knowledge of infection status is essential. All current oral medications used for PrEP have activity against hepatitis B. Incomplete adherence to or abrupt discontinuation of oral PrEP could precipitate a hepatitis B flare. Hepatitis B surface antigen should be tested at the time of PrEP initiation, although PrEP can begin while testing is in process.

Continue to: How to use PrEP

 

 

How to use PrEP

At PrEP initiation, acute or chronic HIV infection must be excluded with a documented negative HIV antigen/antibody test within 1 week of prescribing PrEP.⁵ The CDC guidelines provide an updated HIV testing algorithm (www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf, p 30-31, Figures 4a and 4b), which considers whether patients have received PrEP recently.

Patients with recent high-risk exposures or symptoms of acute HIV at the time of desired PrEP initiation should have an HIV-1 viral load checked with negative results before PrEP is prescribed. Additional criteria for PrEP include weight > 35 kg; screening for hepatitis B virus infection; screening for drug interactions; and drug-specific eCrCl cutoffs of > 60 mL/min for Truvada, > 30 mL/min for Descovy, and > 15 mL/min for Apretude.⁵

Studies regarding time to medication effectiveness are limited. Pharmacokinetic studies of Truvada demonstrate sufficient drug concentrations should be present in peripheral blood mononuclear cells and rectal tissue within 7 days of initiation of oral dosing and around 20 days in vaginal tissue.

Of note, while expedited partner therapy is used as a harm-reduction strategy to treat the sexual partners of patients diagnosed with certain STIs, PrEP is not recommended to be used in this way.

Ongoing monitoring with PrEP. Once oral PrEP is started, STI risk assessment and HIV testing via 4th generation antibody/antigen­ test should be completed at least every 3 months. PrEP oral prescription refills should be limited to 3 months. For patients receiving IM PrEP (Apretude), HIV testing via viral load and antibody/antigen testing should be done at the time of each injection (every 2 months).⁵

Continue to: With oral PrEP...

With oral PrEP, renal function should be checked every 6 months in patients older than 50 years or those with eCrCl < 90 mL/min at initiation. For patients younger than 50 years with no baseline renal dysfunction, the latest guidelines now recommend monitoring every 12 months instead of 6 months.⁵

For patients on Descovy, a lipid panel is recommended at PrEP initiation and every 12 months. Testing for other STIs can be considered on this schedule, based on clinical assessment. The TABLE⁵ summarizes recommended monitoring for patients taking oral PrEP.

Recommended follow-up provides an opportunity to have frequent contact with a potentially high-risk population, and PrEP should be one part of a comprehensive HIV prevention and risk reduction plan. Many patients at high risk for HIV acquisition may benefit from frequent follow-up to address screening, referral, and treatment of substance use disorders, mental health conditions, and chronic medical conditions (including hepatitis C infection) and provide ongoing preventive health care. 

Special uses of PrEP 

Same-day PrEP. Starting PrEP on the day of the initial appointment may be appropriate based on patient risk factors and barriers to care, such as a high risk for contracting HIV before the subsequent appointment for a prescription of PrEP or an inability to return to the clinic in a timely fashion due to transportation or work constraints, or clinician availability. For these patients, assuming there is a low concern for acute or chronic HIV infection, PrEP can be initiated on the day of the initial visit.⁵

In these cases, point-of-care HIV and creatinine testing with same-day results should be completed. Antigen/antibody fingerstick testing or HIV-1 RNA test are preferred; oral fluid HIV testing should not be used for same-day PrEP due to its lower sensitivity for HIV detection. If same-day testing is unavailable, blood should be drawn at the visit so that HIV and creatinine testing can be completed as soon as possible.

Continue to: In addition to initial laboratory testing...

In addition to initial laboratory testing, clinics offering same-day PrEP should be able to provide: (1) assistance for patients to enroll in health insurance or a medication assistance program (eg, Ready, Set, PrEP) for those ineligible for insurance coverage, (2) rapid follow-­up on all laboratory results with reliable patient contact information, and (3) follow-up appointments with clinicians able to prescribe and administer PrEP medications.

Off-label “on-demand” PrEP. An off-label treatment regimen for men who have sex with men (MSM) is termed “on-demand” PrEP or “2-1-1 PrEP” and is included in the CDC guidelines for consideration by clinicians.⁵ This alternative dosing schedule can be used for individuals who have sex less frequently and in a more planned fashion.

On-demand PrEP requires a patient to take 2 tablets of Truvada 2 to 24 hours before sex, followed by 1 tablet 24 hours and 1 tablet 48 hours after sexual activity. If a sexual act occurs at 48 hours, the patient should extend the daily dose for 48 additional hours, such that PrEP is always used daily for 48 hours after the last sex act.

This method has been studied with Truvada in MSM in Europe and Canada through the IPERGAY and PREVENIR trials and shown to have ≥ 86% efficacy in preventing HIV acquisition.^11,12 The only US-based study showed lower efficacy; however, based on the currently available data, the International Antiviral Society-USA Panel has recommended it as an alternative regimen.^13,14

PrEP via telehealth. Visits for PrEP initiation and continuation can be completed via telehealth.⁵ Patients then can complete necessary laboratory tests by going to a physical laboratory location or using mailed specimen kits in which they can self-collect urine, oral/rectal swabs, and fingerstick blood samples.

Continue to: PrEP use in specific populations

 

 

PrEP use in specific populations

Adolescents

Truvada, Descovy, and Apretude all are now approved for use in adolescents weighing ≥ 35 kg. Two important considerations when prescribing to this population are the effects of Truvada on bone health and the unique barriers to access.

In studies of adolescent MSM using Truvada for PrEP, bone mineral density declined, especially among those ages 15 to 19 years.¹⁵ As such, the clinical impact of decreased bone mineral density should be weighed against the risk for HIV acquisition; however, bone mineral density monitoring is not recommended in the current guidelines. CDC guidelines suggest considering Descovy for male adolescents given its potential lower impact on bone mineral density.⁵

Confidentiality and legal issues exist when prescribing PrEP to minors. In terms of parental/guardian involvement, clinicians who are prescribing PrEP for patients younger than 18 years should consult the CDC website for guidance on local and state regulations that govern prescribing and confidentiality (www.cdc.gov/hiv/policies/law/states/­minors.html).

CDC guidelines suggest considering Descovy for male adolescents given its potential lower impact on bone mineral density.

Insurance billing statements may lead to inadvertent disclosure of a minor’s decision to take PrEP to their legal guardian.¹⁶ Generic Truvada costs less than $100 for a 3-month supply when using goodrx.com, which may offer an alternative to insurance for medication payment. 

Peripartum patients

The increased risk for HIV acquisition in the peripartum period for female patients is well documented.¹⁷ Guidelines recommend offering PrEP with Truvada to female patients at risk for conception, currently pregnant, or breastfeeding when that patient’s partner has HIV and the partner’s viral load is unknown or detectable. Descovy is not recommended for pregnant or breastfeeding patients.⁵ Cabotegravir­-containing regimens (Apretude) have not been approved by the FDA for pregnant or breastfeeding patients.⁵

Continue to: Data on the impact of...

Data on the impact of Truvada for PrEP on fetal health are still emerging. A large study in Kenya showed no significant differences in preterm birth, low birth weight, or early infant growth, and a randomized, noninferiority trial in South Africa showed no association between Truvada for PrEP and preterm birth or the birth of small-for-­gestational-age infants.^18,19 There are no definitive studies of breastfeeding infants exposed to Truvada, but data from previous trials of breastfeeding mothers who were taking the individual components that are combined in the Truvada pill indicated there is minimal medication exposure to the infant.⁵

PrEP studies in the peripartum period to date have been conducted exclusively among cisgender women, and data do not yet reflect the experiences of transgender men, genderqueer people, and nonbinary individuals in the peripartum period.⁵

Transgender people

Transgender women should be strongly considered candidates for PrEP as they are at an extremely high risk for HIV acquisition. The most recent National HIV Behavioral Surveillance survey found that approximately 42% of transgender women were living with HIV.²⁰ The survey revealed stark racial and ethnic disparities among transgender women living with HIV: 62% identified as Black/African American, compared with 35% Hispanic/Latina and 17% White.²⁰

Transgender women report high rates of sexual assault, unprotected receptive anal sex, commercial sex work, homelessness, mental health disorders, and substance use, putting them at increased risk for HIV acquisition.²¹ However, transgender women are less likely to have discussed PrEP with a clinician, are less likely to be on PrEP even when interested in starting, and have higher rates of medication nonadherence compared with cisgender MSM.^21,22 PrEP has not been found to decrease levels of feminizing hormones; however, studies are mixed as to whether feminizing hormones decrease Truvada concentrations in rectal mucosa, so clinicians should emphasize the importance of daily medication adherence.²³

Transgender men have not been included in any PrEP trials, so no specific recommendations are available. 

Continue to: Disparities in PrEP access and use exist

 

 

Disparities in PrEP access and use exist

The lifetime risk for HIV acquisition is 9% among White MSM, 50% among Black MSM, and 20% among Hispanic MSM.²⁴ Despite this large disparity in disease burden, Black and Hispanic individuals are less likely to be aware of PrEP, have discussed PrEP with a health care professional, or used PrEP compared with their White counterparts.²⁵ As a result, in 2020, PrEP coverage for eligible White individuals was 61%, while coverage among eligible Black and Hispanic/Latino individuals was just 8% and 14%, respectively.²⁶

Rural areas have been shown to lag behind urban areas in PrEP awareness and use.

Surveillance data comparing male and female PrEP coverage reveal further disparities between the sexes, with PrEP coverage for eligible female-at-birth patients estimated to be 9% compared with 25.8% for male-at-birth patients.²⁶ The gap between the risk for HIV infection and the access to and uptake of PrEP coverage is most pronounced among Black women, for whom the rate of new HIV diagnosis is > 10 times higher than it is for White women, but who have some of the lowest awareness and utilization rates of all demographics.²⁷

The rural population at risk. Disparities in HIV awareness and PrEP use also exist between rural and urban populations, as well as by health insurance status. Rural areas have been shown to lag behind urban areas in PrEP awareness and use. Two potential explanations for this disparity are differences­ in HIV- and drug use–associated stigma and health insurance status. Greater stigma against drug use and HIV in rural areas has been associated with lower rates of PrEP use.²⁸

Individuals younger than 65 years in rural areas are less likely to have private health insurance and more likely to be uninsured compared with their urban counterparts, which may impact access to clinicians knowledgeable about PrEP.²⁹ Notably, MSM who live in states that have expanded Medicaid have higher rates of PrEP use compared with MSM living in states that have not expanded Medicaid.³⁰

Health insurers in the United States are required to cover PrEP medication, clinician visits, and associated blood work with no patient cost-sharing, although implementation barriers such as prior authorizations still exist. 

Conclusion

Family physicians are well positioned to identify patients at risk for HIV infection, prescribe PrEP, organize comprehensive follow-up care, and partner with their health systems and local communities to reduce barriers to care. Those who can leverage existing relationships with local health departments, school-based health clinics, congregate housing programs, LGBTQIA+ advocacy groups, harm-reduction coalitions, and other community-based organizations to raise PrEP awareness play a critical role in preventing HIV transmission and reducing health care disparities in their communities.

CORRESPONDENCE
Andrew V.A. Foley, MD, MPH, Erie Family Health Centers, 2418 W Division Street, Chicago, IL 60622; [email protected]

Further details from the phase 2b AZALEA trial with the factor XI inhibitor abelacimab (Anthos) show significant reductions in major and clinically relevant nonmajor bleeding, compared with rivaroxaban, for patients with atrial fibrillation (AFib); the risk of stroke was moderate to high.

The trial was stopped earlier this year because of an “overwhelming” reduction in bleeding with abelacimab in comparison to rivaroxaban. Abelacimab is a monoclonal antibody given by subcutaneous injection once a month.

“Details of the bleeding results have now shown that the 150-mg dose of abelacimab, which is the dose being carried forward to phase 3 trials, was associated with a 67% reduction in major or clinically relevant nonmajor bleeding, the primary endpoint of the study.”

In addition, major bleeding was reduced by 74%, and major gastrointestinal bleeding was reduced by 93%.

“We are seeing really profound reductions in bleeding with this agent vs. a NOAC [novel oral anticoagulant],” lead AZALEA investigator Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, said in an interview.

“Major bleeding – effectively the type of bleeding that results in hospitalization – is reduced by more than two-thirds, and major GI bleeding – which is the most common type of bleeding experienced by AF patients on anticoagulants – is almost eliminated. This gives us real hope that we have finally found an anticoagulant that is remarkably safe and will allow us to use anticoagulation in our most vulnerable patients,” he said.

Dr. Ruff presented the full results from the AZALEA trial at the American Heart Association scientific sessions.

He noted that AFib is one of the most common medical conditions in the world and that it confers an increased risk of stroke. Anticoagulants reduce this risk very effectively, and while the NOACS, such as apixaban and rivaroxaban, are safer than warfarin, significant bleeding still occurs, and “shockingly,” he said, between 30% and 60% of patients are not prescribed an anticoagulant or discontinue treatment because of bleeding concerns.

“Clearly, we need safer anticoagulants to protect these patients. Factor XI inhibitors, of which abelacimab is one, have emerged as the most promising agents, as they are thought to provide precision anticoagulation,” Dr. Ruff said.

He explained that factor XI appears to be involved in the formation of thrombus, which blocks arteries and causes strokes and myocardial infarction (thrombosis), but not in the healing process of blood vessels after injury (hemostasis). So, it is believed that inhibiting factor XI should reduce thrombotic events without causing excess bleeding.

AZALEA, which is the largest and longest trial of a factor XI inhibitor to date, enrolled 1,287 adults with AF who were at moderate to high risk of stroke.

They were randomly assigned to receive one of three treatments: oral rivaroxaban 20 mg daily; abelacimab 90 mg; or abelacimab 150 mg. Abelacimab was given monthly by injection.

Both doses of abelacimab inhibited factor XI almost completely; 97% inhibition was achieved with the 90-mg dose, and 99% inhibition was achieved with the 150-mg dose.

Results showed that after a median follow-up of 1.8 years, there was a clear reduction in all bleeding endpoints with both doses of abelacimab, compared with rivaroxaban.

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

Further details from the phase 2b AZALEA trial with the factor XI inhibitor abelacimab (Anthos) show significant reductions in major and clinically relevant nonmajor bleeding, compared with rivaroxaban, for patients with atrial fibrillation (AFib); the risk of stroke was moderate to high.

The trial was stopped earlier this year because of an “overwhelming” reduction in bleeding with abelacimab in comparison to rivaroxaban. Abelacimab is a monoclonal antibody given by subcutaneous injection once a month.

“Details of the bleeding results have now shown that the 150-mg dose of abelacimab, which is the dose being carried forward to phase 3 trials, was associated with a 67% reduction in major or clinically relevant nonmajor bleeding, the primary endpoint of the study.”

In addition, major bleeding was reduced by 74%, and major gastrointestinal bleeding was reduced by 93%.

“We are seeing really profound reductions in bleeding with this agent vs. a NOAC [novel oral anticoagulant],” lead AZALEA investigator Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, said in an interview.

“Major bleeding – effectively the type of bleeding that results in hospitalization – is reduced by more than two-thirds, and major GI bleeding – which is the most common type of bleeding experienced by AF patients on anticoagulants – is almost eliminated. This gives us real hope that we have finally found an anticoagulant that is remarkably safe and will allow us to use anticoagulation in our most vulnerable patients,” he said.

Dr. Ruff presented the full results from the AZALEA trial at the American Heart Association scientific sessions.

He noted that AFib is one of the most common medical conditions in the world and that it confers an increased risk of stroke. Anticoagulants reduce this risk very effectively, and while the NOACS, such as apixaban and rivaroxaban, are safer than warfarin, significant bleeding still occurs, and “shockingly,” he said, between 30% and 60% of patients are not prescribed an anticoagulant or discontinue treatment because of bleeding concerns.

“Clearly, we need safer anticoagulants to protect these patients. Factor XI inhibitors, of which abelacimab is one, have emerged as the most promising agents, as they are thought to provide precision anticoagulation,” Dr. Ruff said.

He explained that factor XI appears to be involved in the formation of thrombus, which blocks arteries and causes strokes and myocardial infarction (thrombosis), but not in the healing process of blood vessels after injury (hemostasis). So, it is believed that inhibiting factor XI should reduce thrombotic events without causing excess bleeding.

AZALEA, which is the largest and longest trial of a factor XI inhibitor to date, enrolled 1,287 adults with AF who were at moderate to high risk of stroke.

They were randomly assigned to receive one of three treatments: oral rivaroxaban 20 mg daily; abelacimab 90 mg; or abelacimab 150 mg. Abelacimab was given monthly by injection.

Both doses of abelacimab inhibited factor XI almost completely; 97% inhibition was achieved with the 90-mg dose, and 99% inhibition was achieved with the 150-mg dose.

Results showed that after a median follow-up of 1.8 years, there was a clear reduction in all bleeding endpoints with both doses of abelacimab, compared with rivaroxaban.

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

Further details from the phase 2b AZALEA trial with the factor XI inhibitor abelacimab (Anthos) show significant reductions in major and clinically relevant nonmajor bleeding, compared with rivaroxaban, for patients with atrial fibrillation (AFib); the risk of stroke was moderate to high.

The trial was stopped earlier this year because of an “overwhelming” reduction in bleeding with abelacimab in comparison to rivaroxaban. Abelacimab is a monoclonal antibody given by subcutaneous injection once a month.

“Details of the bleeding results have now shown that the 150-mg dose of abelacimab, which is the dose being carried forward to phase 3 trials, was associated with a 67% reduction in major or clinically relevant nonmajor bleeding, the primary endpoint of the study.”

In addition, major bleeding was reduced by 74%, and major gastrointestinal bleeding was reduced by 93%.

“We are seeing really profound reductions in bleeding with this agent vs. a NOAC [novel oral anticoagulant],” lead AZALEA investigator Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, said in an interview.

“Major bleeding – effectively the type of bleeding that results in hospitalization – is reduced by more than two-thirds, and major GI bleeding – which is the most common type of bleeding experienced by AF patients on anticoagulants – is almost eliminated. This gives us real hope that we have finally found an anticoagulant that is remarkably safe and will allow us to use anticoagulation in our most vulnerable patients,” he said.

Dr. Ruff presented the full results from the AZALEA trial at the American Heart Association scientific sessions.

He noted that AFib is one of the most common medical conditions in the world and that it confers an increased risk of stroke. Anticoagulants reduce this risk very effectively, and while the NOACS, such as apixaban and rivaroxaban, are safer than warfarin, significant bleeding still occurs, and “shockingly,” he said, between 30% and 60% of patients are not prescribed an anticoagulant or discontinue treatment because of bleeding concerns.

“Clearly, we need safer anticoagulants to protect these patients. Factor XI inhibitors, of which abelacimab is one, have emerged as the most promising agents, as they are thought to provide precision anticoagulation,” Dr. Ruff said.

He explained that factor XI appears to be involved in the formation of thrombus, which blocks arteries and causes strokes and myocardial infarction (thrombosis), but not in the healing process of blood vessels after injury (hemostasis). So, it is believed that inhibiting factor XI should reduce thrombotic events without causing excess bleeding.

AZALEA, which is the largest and longest trial of a factor XI inhibitor to date, enrolled 1,287 adults with AF who were at moderate to high risk of stroke.

They were randomly assigned to receive one of three treatments: oral rivaroxaban 20 mg daily; abelacimab 90 mg; or abelacimab 150 mg. Abelacimab was given monthly by injection.

Both doses of abelacimab inhibited factor XI almost completely; 97% inhibition was achieved with the 90-mg dose, and 99% inhibition was achieved with the 150-mg dose.

Results showed that after a median follow-up of 1.8 years, there was a clear reduction in all bleeding endpoints with both doses of abelacimab, compared with rivaroxaban.

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

TOPLINE:

In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.

METHODOLOGY:

• Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).
• Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.
• 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.
• Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.

TAKEAWAY:

• Acamprosate (NNT = 11) and naltrexone (50 mg/day; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.
• Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11), compared with placebo.
• Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, –4.99 days).
• The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.

IN PRACTICE:

“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/day, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.

SOURCE:

The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online in JAMA.

LIMITATIONS:

Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.

DISCLOSURES:

Funding for the study was provided by the Agency for Healthcare Research and Quality of the U.S. Department of Health & Human Services. The authors have disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.

METHODOLOGY:

• Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).
• Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.
• 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.
• Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.

TAKEAWAY:

• Acamprosate (NNT = 11) and naltrexone (50 mg/day; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.
• Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11), compared with placebo.
• Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, –4.99 days).
• The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.

IN PRACTICE:

“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/day, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.

SOURCE:

The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online in JAMA.

LIMITATIONS:

Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.

DISCLOSURES:

Funding for the study was provided by the Agency for Healthcare Research and Quality of the U.S. Department of Health & Human Services. The authors have disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In conjunction with psychosocial interventions, oral naltrexone and acamprosate are both effective first-line drug therapies for alcohol use disorder (AUD), results of a systematic review and meta-analysis found.

METHODOLOGY:

• Researchers evaluated efficacy and comparative efficacy of three therapies for AUD that are approved in the United States (acamprosate, naltrexone, and disulfiram) and six that are commonly used off-label (baclofen, gabapentin, varenicline, topiramate, prazosin, and ondansetron).
• Data came from 118 randomized clinical trials lasting at least 12 weeks with 20,976 participants.
• 74% of these studies included psychosocial co-interventions, and the primary outcome was alcohol consumption.
• Numbers needed to treat (NNT) were calculated for medications with at least moderate strength of evidence for benefit.

TAKEAWAY:

• Acamprosate (NNT = 11) and naltrexone (50 mg/day; NNT = 18) had the highest strength of evidence and were both associated with statistically significant improvement in drinking outcomes.
• Oral naltrexone but not acamprosate was also associated with lower rates of return to heavy drinking (NNT = 11), compared with placebo.
• Injectable naltrexone was not associated with return to any or heavy drinking but was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, –4.99 days).
• The four trials that directly compared acamprosate with oral naltrexone did not consistently establish superiority of either medication for alcohol use outcomes, and among off-label drugs, only topiramate had moderate strength of evidence for benefit.

IN PRACTICE:

“Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone, 50 mg/day, and acamprosate as first-line pharmacotherapies for alcohol use disorder,” the authors write.

SOURCE:

The study, with first author Melissa McPheeters, PhD, MPH, RTI International, Research Triangle Park, North Carolina, was published online in JAMA.

LIMITATIONS:

Most study participants had moderate to severe AUD, and the applicability of the findings to people with mild AUD is uncertain. The mean age of participants was typically between ages 40 and 49 years, and it’s unclear whether the medications have similar efficacy for older or younger age groups. Information on adverse effects was limited.

DISCLOSURES:

Funding for the study was provided by the Agency for Healthcare Research and Quality of the U.S. Department of Health & Human Services. The authors have disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.

METHODOLOGY:

• This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
• Incident cases of dementia were determined through linkage from multiple databases.
• Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.

TAKEAWAY:

• During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
• Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
• Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
• After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.

IN PRACTICE:

“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.

SOURCE:

The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.

LIMITATIONS:

Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.

DISCLOSURES:

The study had no commercial funding. The authors have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.

METHODOLOGY:

• This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
• Incident cases of dementia were determined through linkage from multiple databases.
• Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.

TAKEAWAY:

• During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
• Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
• Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
• After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.

IN PRACTICE:

“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.

SOURCE:

The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.

LIMITATIONS:

Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.

DISCLOSURES:

The study had no commercial funding. The authors have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.

METHODOLOGY:

• This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
• Incident cases of dementia were determined through linkage from multiple databases.
• Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.

TAKEAWAY:

• During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
• Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
• Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
• After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.

IN PRACTICE:

“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.

SOURCE:

The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.

LIMITATIONS:

Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.

DISCLOSURES:

The study had no commercial funding. The authors have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Respiratory syncytial virus (RSV) is a negative-sense, single-stranded, ribonucleic acid (RNA) virus that is a member of Pneumoviridae family. Two subtypes, A and B, and multiple genotypes circulate during fall and winter seasonal outbreaks of RSV.¹ RSV can cause severe lower respiratory tract disease including bronchiolitis, pneumonia, respiratory failure, and death. Each year, RSV disease causes the hospitalization of 1.5% to 2% of children younger than 6 months of age, resulting in 100 to 300 deaths.² For infants younger than 1 year, RSV infection is the leading cause of hospitalization.³ In 2023, two new treatments have become available to prevent RSV disease: nirsevimab and RSVPreF vaccine. 

Nirsevimab

Nirsevimab is an antibody to an RSV antigen. It has a long half-life and is approved for administration to infants, providing passive immunization. In contrast, administration of the RSVPreF vaccine to pregnant persons elicits active maternal immunity, resulting in the production of anti-RSV antibodies that are transferred to the fetus, resulting in passive immunity in the infant. Seasonal administration of nirsevimab and the RSV vaccine maximizes benefit to the infant and conserves limited health care resources. In temperate regions in the United States, the RSV infection season typically begins in October and peaks in December through mid-February and ends in April or May.^4,5 In southern Florida, the RSV season often begins in August to September, peaks in November through December, and ends in March.^4,5 

This editorial reviews 3 strategies for prevention of RSV infection in infants, including: 

• universal treatment of newborns with nirsevimab
• immunization of pregnant persons with an RSVpreF vaccine in the third trimester appropriately timed to occur just before the beginning or during RSV infection season
• prioritizing universal maternal RSV vaccination with reflex administration of nirsevimab to newborns when the pregnant person was  not vaccinated.⁶ 

Of note, there are no studies that have evaluated the effectiveness of combining RSVpreF vaccine and nirsevimab. The Centers for Disease Control and Prevention (CDC) does not recommend combining both RSV vaccination of pregnant persons plus nirsevimab treatment of the infant, except in limited circumstances, such as for immunocompromised pregnant people with limited antibody production or newborns who have a massive transfusion, which dilutes antibody titres.⁶ 

RSV prevention strategy 1

Universal treatment of newborns and infants  with nirsevimab 

Nirsevimab (Beyfortus, Sanofi and AstraZeneca) is an IgG 1-kappa monoclonal antibody with a long half-life that targets the prefusion conformation of the RSV F-protein, resulting in passive immunity to infection.7 Passive immunization results in rapid protection against infection because it does not require activation of the immune system. Nirsevimab is long acting due to amino acid substitutions in the Fc region, increasing binding to the neonatal Fc receptor, which protects IgG antibodies from degradation, thereby extending the antibody half-life. The terminal halflife of nirsevimab is 71 days, and the duration of protection following a single dose is at least 5 months. 

Nirsevimab is approved by the US Food and Drug Administration (FDA) for all neonates and infants born or entering their first RSV infection season and for children up to  24 months of age who are vulnerable to severe RSV during their second RSV infection season. For infants born outside the RSV infection season, nirsevimab should be administered once prior to the start of the next RSV infection season.⁷ Nirsevimab is administered as a single intramuscular injection at a dose of  50 mg for neonates and infants < 5 kg  in weight and a dose of 100 mg for neonates and infants ≥ 5 kg in weight.⁷ The list average wholesale price for both doses is $594.⁸  Nirsevimab is contraindicated for patients with a serious hypersensitivity reaction to nirsevimab or its excipients.⁷ In clinical trials, adverse reactions including rash and injection site reaction were reported in 1.2% of participants.7 Some RSV variants may be resistant to neutralization with nirsevimab.^7,9 

In a randomized clinical trial, 1,490 infants born ≥ 35 weeks’ gestation, the rates of medically-attended RSV lower respiratory tract disease (MA RSV LRTD) through 150 days of follow-up in the placebo and nirsevimab groups were 5.0% and 1.2%, respectively (P < .001).^7,10 Compared with placebo, nirsevimab reduced hospitalizations due to RSV LRTD by 60% through 150 days of follow up. In a randomized clinical trial enrolling 1,453 infants born between 29 weeks’ and < 35 weeks’ gestation, the rates of MA RSV LRTD through 150 days of follow up in the placebo and nirsevimab groups were 9.5% and 2.6%, respectively  (P < .001). In this study of infants born preterm, compared with placebo, nirsevimab reduced hospitalization due to RSV LRTD by 70% through 150 days of follow up.⁷ Nirsevimab is thought to be cost-effective at the current price per dose, but more data are needed to precisely define the magnitude of the health care savings associated with universal nirsevimab administration.^11-13 The CDC reports that the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of nirsevimab administration to infants is approximately $250,000, given an estimated cost of $500 for one dose of vaccine.¹⁴ 

Universal passive vaccination of newborns is recommended by many state departments of public health, which can provide the vaccine without cost to clinicians and health care facilities participating in the children’s vaccination program.

Continue to: RSV prevention strategy 2...

RSV prevention strategy 2

Universal RSV vaccination of pregnant persons from September through January 

The RSVpreF vaccine (Abryvso, Pfizer) is approved by the FDA for the active immunization of pregnant persons between 32 through 36 weeks’ gestation for the prevention of RSV LRTD in infants from birth through 6 months of age.¹⁵ Administration of the RSVpreF vaccine to pregnant people elicits the formation of antiRSV antibodies that are transferred transplacentally to the fetus, resulting in the protection of the infant from RSV during the first 6 months of life. The RSVpreF vaccine also is approved to prevent RSV LRTD in people aged ≥ 60 years. 

The RSVpreF vaccine contains the prefusion form of the RSV fusion (F) protein responsible for viral entry into host cells. The vaccine contains 60 µg of both RSV preF A and preF B recombinant proteins. The vaccine is administered as a single intramuscular dose in a volume of 0.5 mL. The vaccine is provided in a vial in a lyophilized form and must be reconstituted prior to administration. The average wholesale price of RSVPreF vaccine is $354.¹⁶ The vaccine is contraindicated for people who have had an allergic reaction to any component of the vaccine. The most commonly reported adverse reaction is injection site pain (41%).¹⁵ The FDA reports a “numerical imbalance in preterm births in Abrysvo recipients compared to placebo recipients” (5.7% vs 4.7%), and “available data are insufficient to establish or exclude a causal relationship between preterm birth and Abrysvo.”¹⁵ In rabbits there is no evidence of developmental toxicity and congenital anomalies associated with the RSVpreF vaccine. In human studies, no differences in the rate of congenital anomalies or fetal deaths were noted between RSVpreF vaccine and placebo.

 In a clinical trial, 6,975 pregnant participants 24 through  36 weeks’ gestation were randomly assigned to receive a placebo or the RSVpreF vaccine.^15,17 After birth, follow-up of infants at 180 days, showed that the rates of MA RSV LRTD among the infants in the placebo and RSVpreF vaccine groups were 3.4% and 1.6%, respectively. At 180 days, the reported rates of severe RSV LRTD in the placebo and RSVpreF vaccine groups were 1.8% and 0.5%, respectively. In this study, among the subset of pregnant participants who received the RSVpreF vaccine (n = 1,572) or placebo  (n = 1,539) at 32 through 36 weeks’ gestation, the rates of MA RSV LRTD among the infants in the placebo and RSVpreF vaccine groups were 3.6% and 1.5%, respectively. In the subset of pregnant participants vaccinated at 32 through 36 weeks’ gestation, at 180 days postvaccination, the reported rates of severe RSV LRTD in the placebo and RSVpreF vaccine groups were 1.6% and  0.4%, respectively.¹⁵ 

The CDC has recommended that the RSVpreF vaccine be administered to pregnant people 32 through 36 weeks’ gestation from September through the end of January in most of the continental United States to reduce the rate of RSV LRTD in infants.⁶ September was selected because it is 1 to 2 months before the start of the RSV season, and it takes at least 14 days for maternal vaccination to result in transplacental transfer of protective antibodies to the fetus. January was selected because it is 2 to 3 months before the anticipated end of the RSV season.⁶ The CDC also noted that, for regions with a different pattern of RSV seasonality, clinicians should follow the guidance of local public health officials. This applies to the states of Alaska, southern Florida, Hawaii, and Puerto Rico.6 The CDC recommended that infants born < 34 weeks’ gestation should receive nirsevimab.⁶ 

Maternal RSV vaccination is thought to be cost-effective for reducing RSV LRTD in infants. However, the cost-effectiveness analyses are sensitive to the pricing of the two main options: maternal RSV vaccination and nirsevimab.

It is estimated that nirsevimab may provide greater protection than maternal RSV vaccination from RSV LRTD, but the maternal RSVpreF vaccine is priced lower than nirsevimab.¹⁸ Focusing administration of RSVpreF vaccine from September through January of the RSV infection season is thought to maximize benefits to infants and reduce total cost of the vaccination program.¹⁹ With year-round RSVpreF vaccine dosing, the estimated ICER per quality-adjusted life-year (QALY) is approximately $400,000, whereas seasonal dosing reduces the cost to approximately $170,000.¹⁹ 

RSV prevention strategy 3

Vaccinate pregnant persons; reflex to newborn treatment with nirsevimab if maternal RSV vaccination did not occur

RSVpreF vaccination to all pregnant persons 32 through 36 weeks’ gestation during RSV infection season is not likely to result in 100% adherence. For instance, in a CDC-conducted survey only 47% of pregnant persons received an influenza vaccine.2 Newborns whose mothers did not receive an RSVpreF vaccine will need to be considered for treatment with nirsevimab. Collaboration and communication among obstetricians and pediatricians will be needed to avoid miscommunication and missed opportunities to treat newborns during the birth hospitalization. Enhancements in electronic health records, linking the mother’s vaccination record with the newborn’s medical record plus an added feature of electronic alerts when the mother did not receive an appropriately timed RSVpreF vaccine would improve the communication of important clinical information to the pediatrician. 

Next steps for the upcoming peak  RSV season

We are currently in the 2023–2024 RSV infection season and can expect a peak in cases of RSV between December 2023 and February 2024. The CDC recommends protecting all infants against RSV-associated LRTD. The options are to administer the maternal RSVpreF vaccine to pregnant persons or treating the infant with nirsevimab. The vaccine is just now becoming available for administration in regional pharmacies, physician practices, and health systems. Obstetrician-gynecologists should follow the recommendation of their state department of public health. As noted above, many state departments of public health are recommending that all newborns receive nirsevimab. For clinicians in those states, RSVPreF vaccination of pregnant persons is not a priority. ●

Respiratory syncytial virus (RSV) is a negative-sense, single-stranded, ribonucleic acid (RNA) virus that is a member of Pneumoviridae family. Two subtypes, A and B, and multiple genotypes circulate during fall and winter seasonal outbreaks of RSV.¹ RSV can cause severe lower respiratory tract disease including bronchiolitis, pneumonia, respiratory failure, and death. Each year, RSV disease causes the hospitalization of 1.5% to 2% of children younger than 6 months of age, resulting in 100 to 300 deaths.² For infants younger than 1 year, RSV infection is the leading cause of hospitalization.³ In 2023, two new treatments have become available to prevent RSV disease: nirsevimab and RSVPreF vaccine. 

Nirsevimab

Nirsevimab is an antibody to an RSV antigen. It has a long half-life and is approved for administration to infants, providing passive immunization. In contrast, administration of the RSVPreF vaccine to pregnant persons elicits active maternal immunity, resulting in the production of anti-RSV antibodies that are transferred to the fetus, resulting in passive immunity in the infant. Seasonal administration of nirsevimab and the RSV vaccine maximizes benefit to the infant and conserves limited health care resources. In temperate regions in the United States, the RSV infection season typically begins in October and peaks in December through mid-February and ends in April or May.^4,5 In southern Florida, the RSV season often begins in August to September, peaks in November through December, and ends in March.^4,5 

This editorial reviews 3 strategies for prevention of RSV infection in infants, including: 

• universal treatment of newborns with nirsevimab
• immunization of pregnant persons with an RSVpreF vaccine in the third trimester appropriately timed to occur just before the beginning or during RSV infection season
• prioritizing universal maternal RSV vaccination with reflex administration of nirsevimab to newborns when the pregnant person was  not vaccinated.⁶ 

Of note, there are no studies that have evaluated the effectiveness of combining RSVpreF vaccine and nirsevimab. The Centers for Disease Control and Prevention (CDC) does not recommend combining both RSV vaccination of pregnant persons plus nirsevimab treatment of the infant, except in limited circumstances, such as for immunocompromised pregnant people with limited antibody production or newborns who have a massive transfusion, which dilutes antibody titres.⁶ 

RSV prevention strategy 1

Universal treatment of newborns and infants  with nirsevimab 

Nirsevimab (Beyfortus, Sanofi and AstraZeneca) is an IgG 1-kappa monoclonal antibody with a long half-life that targets the prefusion conformation of the RSV F-protein, resulting in passive immunity to infection.7 Passive immunization results in rapid protection against infection because it does not require activation of the immune system. Nirsevimab is long acting due to amino acid substitutions in the Fc region, increasing binding to the neonatal Fc receptor, which protects IgG antibodies from degradation, thereby extending the antibody half-life. The terminal halflife of nirsevimab is 71 days, and the duration of protection following a single dose is at least 5 months. 

Nirsevimab is approved by the US Food and Drug Administration (FDA) for all neonates and infants born or entering their first RSV infection season and for children up to  24 months of age who are vulnerable to severe RSV during their second RSV infection season. For infants born outside the RSV infection season, nirsevimab should be administered once prior to the start of the next RSV infection season.⁷ Nirsevimab is administered as a single intramuscular injection at a dose of  50 mg for neonates and infants < 5 kg  in weight and a dose of 100 mg for neonates and infants ≥ 5 kg in weight.⁷ The list average wholesale price for both doses is $594.⁸  Nirsevimab is contraindicated for patients with a serious hypersensitivity reaction to nirsevimab or its excipients.⁷ In clinical trials, adverse reactions including rash and injection site reaction were reported in 1.2% of participants.7 Some RSV variants may be resistant to neutralization with nirsevimab.^7,9 

In a randomized clinical trial, 1,490 infants born ≥ 35 weeks’ gestation, the rates of medically-attended RSV lower respiratory tract disease (MA RSV LRTD) through 150 days of follow-up in the placebo and nirsevimab groups were 5.0% and 1.2%, respectively (P < .001).^7,10 Compared with placebo, nirsevimab reduced hospitalizations due to RSV LRTD by 60% through 150 days of follow up. In a randomized clinical trial enrolling 1,453 infants born between 29 weeks’ and < 35 weeks’ gestation, the rates of MA RSV LRTD through 150 days of follow up in the placebo and nirsevimab groups were 9.5% and 2.6%, respectively  (P < .001). In this study of infants born preterm, compared with placebo, nirsevimab reduced hospitalization due to RSV LRTD by 70% through 150 days of follow up.⁷ Nirsevimab is thought to be cost-effective at the current price per dose, but more data are needed to precisely define the magnitude of the health care savings associated with universal nirsevimab administration.^11-13 The CDC reports that the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of nirsevimab administration to infants is approximately $250,000, given an estimated cost of $500 for one dose of vaccine.¹⁴ 

Universal passive vaccination of newborns is recommended by many state departments of public health, which can provide the vaccine without cost to clinicians and health care facilities participating in the children’s vaccination program.

Continue to: RSV prevention strategy 2...

RSV prevention strategy 2

Universal RSV vaccination of pregnant persons from September through January 

The RSVpreF vaccine (Abryvso, Pfizer) is approved by the FDA for the active immunization of pregnant persons between 32 through 36 weeks’ gestation for the prevention of RSV LRTD in infants from birth through 6 months of age.¹⁵ Administration of the RSVpreF vaccine to pregnant people elicits the formation of antiRSV antibodies that are transferred transplacentally to the fetus, resulting in the protection of the infant from RSV during the first 6 months of life. The RSVpreF vaccine also is approved to prevent RSV LRTD in people aged ≥ 60 years. 

The RSVpreF vaccine contains the prefusion form of the RSV fusion (F) protein responsible for viral entry into host cells. The vaccine contains 60 µg of both RSV preF A and preF B recombinant proteins. The vaccine is administered as a single intramuscular dose in a volume of 0.5 mL. The vaccine is provided in a vial in a lyophilized form and must be reconstituted prior to administration. The average wholesale price of RSVPreF vaccine is $354.¹⁶ The vaccine is contraindicated for people who have had an allergic reaction to any component of the vaccine. The most commonly reported adverse reaction is injection site pain (41%).¹⁵ The FDA reports a “numerical imbalance in preterm births in Abrysvo recipients compared to placebo recipients” (5.7% vs 4.7%), and “available data are insufficient to establish or exclude a causal relationship between preterm birth and Abrysvo.”¹⁵ In rabbits there is no evidence of developmental toxicity and congenital anomalies associated with the RSVpreF vaccine. In human studies, no differences in the rate of congenital anomalies or fetal deaths were noted between RSVpreF vaccine and placebo.

 In a clinical trial, 6,975 pregnant participants 24 through  36 weeks’ gestation were randomly assigned to receive a placebo or the RSVpreF vaccine.^15,17 After birth, follow-up of infants at 180 days, showed that the rates of MA RSV LRTD among the infants in the placebo and RSVpreF vaccine groups were 3.4% and 1.6%, respectively. At 180 days, the reported rates of severe RSV LRTD in the placebo and RSVpreF vaccine groups were 1.8% and 0.5%, respectively. In this study, among the subset of pregnant participants who received the RSVpreF vaccine (n = 1,572) or placebo  (n = 1,539) at 32 through 36 weeks’ gestation, the rates of MA RSV LRTD among the infants in the placebo and RSVpreF vaccine groups were 3.6% and 1.5%, respectively. In the subset of pregnant participants vaccinated at 32 through 36 weeks’ gestation, at 180 days postvaccination, the reported rates of severe RSV LRTD in the placebo and RSVpreF vaccine groups were 1.6% and  0.4%, respectively.¹⁵ 

The CDC has recommended that the RSVpreF vaccine be administered to pregnant people 32 through 36 weeks’ gestation from September through the end of January in most of the continental United States to reduce the rate of RSV LRTD in infants.⁶ September was selected because it is 1 to 2 months before the start of the RSV season, and it takes at least 14 days for maternal vaccination to result in transplacental transfer of protective antibodies to the fetus. January was selected because it is 2 to 3 months before the anticipated end of the RSV season.⁶ The CDC also noted that, for regions with a different pattern of RSV seasonality, clinicians should follow the guidance of local public health officials. This applies to the states of Alaska, southern Florida, Hawaii, and Puerto Rico.6 The CDC recommended that infants born < 34 weeks’ gestation should receive nirsevimab.⁶ 

Maternal RSV vaccination is thought to be cost-effective for reducing RSV LRTD in infants. However, the cost-effectiveness analyses are sensitive to the pricing of the two main options: maternal RSV vaccination and nirsevimab.

It is estimated that nirsevimab may provide greater protection than maternal RSV vaccination from RSV LRTD, but the maternal RSVpreF vaccine is priced lower than nirsevimab.¹⁸ Focusing administration of RSVpreF vaccine from September through January of the RSV infection season is thought to maximize benefits to infants and reduce total cost of the vaccination program.¹⁹ With year-round RSVpreF vaccine dosing, the estimated ICER per quality-adjusted life-year (QALY) is approximately $400,000, whereas seasonal dosing reduces the cost to approximately $170,000.¹⁹ 

RSV prevention strategy 3

Vaccinate pregnant persons; reflex to newborn treatment with nirsevimab if maternal RSV vaccination did not occur

RSVpreF vaccination to all pregnant persons 32 through 36 weeks’ gestation during RSV infection season is not likely to result in 100% adherence. For instance, in a CDC-conducted survey only 47% of pregnant persons received an influenza vaccine.2 Newborns whose mothers did not receive an RSVpreF vaccine will need to be considered for treatment with nirsevimab. Collaboration and communication among obstetricians and pediatricians will be needed to avoid miscommunication and missed opportunities to treat newborns during the birth hospitalization. Enhancements in electronic health records, linking the mother’s vaccination record with the newborn’s medical record plus an added feature of electronic alerts when the mother did not receive an appropriately timed RSVpreF vaccine would improve the communication of important clinical information to the pediatrician. 

Next steps for the upcoming peak  RSV season

We are currently in the 2023–2024 RSV infection season and can expect a peak in cases of RSV between December 2023 and February 2024. The CDC recommends protecting all infants against RSV-associated LRTD. The options are to administer the maternal RSVpreF vaccine to pregnant persons or treating the infant with nirsevimab. The vaccine is just now becoming available for administration in regional pharmacies, physician practices, and health systems. Obstetrician-gynecologists should follow the recommendation of their state department of public health. As noted above, many state departments of public health are recommending that all newborns receive nirsevimab. For clinicians in those states, RSVPreF vaccination of pregnant persons is not a priority. ●

Respiratory syncytial virus (RSV) is a negative-sense, single-stranded, ribonucleic acid (RNA) virus that is a member of Pneumoviridae family. Two subtypes, A and B, and multiple genotypes circulate during fall and winter seasonal outbreaks of RSV.¹ RSV can cause severe lower respiratory tract disease including bronchiolitis, pneumonia, respiratory failure, and death. Each year, RSV disease causes the hospitalization of 1.5% to 2% of children younger than 6 months of age, resulting in 100 to 300 deaths.² For infants younger than 1 year, RSV infection is the leading cause of hospitalization.³ In 2023, two new treatments have become available to prevent RSV disease: nirsevimab and RSVPreF vaccine. 

Nirsevimab

Nirsevimab is an antibody to an RSV antigen. It has a long half-life and is approved for administration to infants, providing passive immunization. In contrast, administration of the RSVPreF vaccine to pregnant persons elicits active maternal immunity, resulting in the production of anti-RSV antibodies that are transferred to the fetus, resulting in passive immunity in the infant. Seasonal administration of nirsevimab and the RSV vaccine maximizes benefit to the infant and conserves limited health care resources. In temperate regions in the United States, the RSV infection season typically begins in October and peaks in December through mid-February and ends in April or May.^4,5 In southern Florida, the RSV season often begins in August to September, peaks in November through December, and ends in March.^4,5 

This editorial reviews 3 strategies for prevention of RSV infection in infants, including: 

• universal treatment of newborns with nirsevimab
• immunization of pregnant persons with an RSVpreF vaccine in the third trimester appropriately timed to occur just before the beginning or during RSV infection season
• prioritizing universal maternal RSV vaccination with reflex administration of nirsevimab to newborns when the pregnant person was  not vaccinated.⁶ 

Of note, there are no studies that have evaluated the effectiveness of combining RSVpreF vaccine and nirsevimab. The Centers for Disease Control and Prevention (CDC) does not recommend combining both RSV vaccination of pregnant persons plus nirsevimab treatment of the infant, except in limited circumstances, such as for immunocompromised pregnant people with limited antibody production or newborns who have a massive transfusion, which dilutes antibody titres.⁶ 

RSV prevention strategy 1

Universal treatment of newborns and infants  with nirsevimab 

Nirsevimab (Beyfortus, Sanofi and AstraZeneca) is an IgG 1-kappa monoclonal antibody with a long half-life that targets the prefusion conformation of the RSV F-protein, resulting in passive immunity to infection.7 Passive immunization results in rapid protection against infection because it does not require activation of the immune system. Nirsevimab is long acting due to amino acid substitutions in the Fc region, increasing binding to the neonatal Fc receptor, which protects IgG antibodies from degradation, thereby extending the antibody half-life. The terminal halflife of nirsevimab is 71 days, and the duration of protection following a single dose is at least 5 months. 

Nirsevimab is approved by the US Food and Drug Administration (FDA) for all neonates and infants born or entering their first RSV infection season and for children up to  24 months of age who are vulnerable to severe RSV during their second RSV infection season. For infants born outside the RSV infection season, nirsevimab should be administered once prior to the start of the next RSV infection season.⁷ Nirsevimab is administered as a single intramuscular injection at a dose of  50 mg for neonates and infants < 5 kg  in weight and a dose of 100 mg for neonates and infants ≥ 5 kg in weight.⁷ The list average wholesale price for both doses is $594.⁸  Nirsevimab is contraindicated for patients with a serious hypersensitivity reaction to nirsevimab or its excipients.⁷ In clinical trials, adverse reactions including rash and injection site reaction were reported in 1.2% of participants.7 Some RSV variants may be resistant to neutralization with nirsevimab.^7,9 

In a randomized clinical trial, 1,490 infants born ≥ 35 weeks’ gestation, the rates of medically-attended RSV lower respiratory tract disease (MA RSV LRTD) through 150 days of follow-up in the placebo and nirsevimab groups were 5.0% and 1.2%, respectively (P < .001).^7,10 Compared with placebo, nirsevimab reduced hospitalizations due to RSV LRTD by 60% through 150 days of follow up. In a randomized clinical trial enrolling 1,453 infants born between 29 weeks’ and < 35 weeks’ gestation, the rates of MA RSV LRTD through 150 days of follow up in the placebo and nirsevimab groups were 9.5% and 2.6%, respectively  (P < .001). In this study of infants born preterm, compared with placebo, nirsevimab reduced hospitalization due to RSV LRTD by 70% through 150 days of follow up.⁷ Nirsevimab is thought to be cost-effective at the current price per dose, but more data are needed to precisely define the magnitude of the health care savings associated with universal nirsevimab administration.^11-13 The CDC reports that the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of nirsevimab administration to infants is approximately $250,000, given an estimated cost of $500 for one dose of vaccine.¹⁴ 

Universal passive vaccination of newborns is recommended by many state departments of public health, which can provide the vaccine without cost to clinicians and health care facilities participating in the children’s vaccination program.

Continue to: RSV prevention strategy 2...

RSV prevention strategy 2

Universal RSV vaccination of pregnant persons from September through January 

The RSVpreF vaccine (Abryvso, Pfizer) is approved by the FDA for the active immunization of pregnant persons between 32 through 36 weeks’ gestation for the prevention of RSV LRTD in infants from birth through 6 months of age.¹⁵ Administration of the RSVpreF vaccine to pregnant people elicits the formation of antiRSV antibodies that are transferred transplacentally to the fetus, resulting in the protection of the infant from RSV during the first 6 months of life. The RSVpreF vaccine also is approved to prevent RSV LRTD in people aged ≥ 60 years. 

The RSVpreF vaccine contains the prefusion form of the RSV fusion (F) protein responsible for viral entry into host cells. The vaccine contains 60 µg of both RSV preF A and preF B recombinant proteins. The vaccine is administered as a single intramuscular dose in a volume of 0.5 mL. The vaccine is provided in a vial in a lyophilized form and must be reconstituted prior to administration. The average wholesale price of RSVPreF vaccine is $354.¹⁶ The vaccine is contraindicated for people who have had an allergic reaction to any component of the vaccine. The most commonly reported adverse reaction is injection site pain (41%).¹⁵ The FDA reports a “numerical imbalance in preterm births in Abrysvo recipients compared to placebo recipients” (5.7% vs 4.7%), and “available data are insufficient to establish or exclude a causal relationship between preterm birth and Abrysvo.”¹⁵ In rabbits there is no evidence of developmental toxicity and congenital anomalies associated with the RSVpreF vaccine. In human studies, no differences in the rate of congenital anomalies or fetal deaths were noted between RSVpreF vaccine and placebo.

 In a clinical trial, 6,975 pregnant participants 24 through  36 weeks’ gestation were randomly assigned to receive a placebo or the RSVpreF vaccine.^15,17 After birth, follow-up of infants at 180 days, showed that the rates of MA RSV LRTD among the infants in the placebo and RSVpreF vaccine groups were 3.4% and 1.6%, respectively. At 180 days, the reported rates of severe RSV LRTD in the placebo and RSVpreF vaccine groups were 1.8% and 0.5%, respectively. In this study, among the subset of pregnant participants who received the RSVpreF vaccine (n = 1,572) or placebo  (n = 1,539) at 32 through 36 weeks’ gestation, the rates of MA RSV LRTD among the infants in the placebo and RSVpreF vaccine groups were 3.6% and 1.5%, respectively. In the subset of pregnant participants vaccinated at 32 through 36 weeks’ gestation, at 180 days postvaccination, the reported rates of severe RSV LRTD in the placebo and RSVpreF vaccine groups were 1.6% and  0.4%, respectively.¹⁵ 

The CDC has recommended that the RSVpreF vaccine be administered to pregnant people 32 through 36 weeks’ gestation from September through the end of January in most of the continental United States to reduce the rate of RSV LRTD in infants.⁶ September was selected because it is 1 to 2 months before the start of the RSV season, and it takes at least 14 days for maternal vaccination to result in transplacental transfer of protective antibodies to the fetus. January was selected because it is 2 to 3 months before the anticipated end of the RSV season.⁶ The CDC also noted that, for regions with a different pattern of RSV seasonality, clinicians should follow the guidance of local public health officials. This applies to the states of Alaska, southern Florida, Hawaii, and Puerto Rico.6 The CDC recommended that infants born < 34 weeks’ gestation should receive nirsevimab.⁶ 

Maternal RSV vaccination is thought to be cost-effective for reducing RSV LRTD in infants. However, the cost-effectiveness analyses are sensitive to the pricing of the two main options: maternal RSV vaccination and nirsevimab.

It is estimated that nirsevimab may provide greater protection than maternal RSV vaccination from RSV LRTD, but the maternal RSVpreF vaccine is priced lower than nirsevimab.¹⁸ Focusing administration of RSVpreF vaccine from September through January of the RSV infection season is thought to maximize benefits to infants and reduce total cost of the vaccination program.¹⁹ With year-round RSVpreF vaccine dosing, the estimated ICER per quality-adjusted life-year (QALY) is approximately $400,000, whereas seasonal dosing reduces the cost to approximately $170,000.¹⁹ 

RSV prevention strategy 3

Vaccinate pregnant persons; reflex to newborn treatment with nirsevimab if maternal RSV vaccination did not occur

RSVpreF vaccination to all pregnant persons 32 through 36 weeks’ gestation during RSV infection season is not likely to result in 100% adherence. For instance, in a CDC-conducted survey only 47% of pregnant persons received an influenza vaccine.2 Newborns whose mothers did not receive an RSVpreF vaccine will need to be considered for treatment with nirsevimab. Collaboration and communication among obstetricians and pediatricians will be needed to avoid miscommunication and missed opportunities to treat newborns during the birth hospitalization. Enhancements in electronic health records, linking the mother’s vaccination record with the newborn’s medical record plus an added feature of electronic alerts when the mother did not receive an appropriately timed RSVpreF vaccine would improve the communication of important clinical information to the pediatrician. 

Next steps for the upcoming peak  RSV season

We are currently in the 2023–2024 RSV infection season and can expect a peak in cases of RSV between December 2023 and February 2024. The CDC recommends protecting all infants against RSV-associated LRTD. The options are to administer the maternal RSVpreF vaccine to pregnant persons or treating the infant with nirsevimab. The vaccine is just now becoming available for administration in regional pharmacies, physician practices, and health systems. Obstetrician-gynecologists should follow the recommendation of their state department of public health. As noted above, many state departments of public health are recommending that all newborns receive nirsevimab. For clinicians in those states, RSVPreF vaccination of pregnant persons is not a priority. ●

SAN DIEGO – Patients with early oligoarticular psoriatic arthritis (PsA) who took apremilast (Otezla) had more than double the response rate of placebo-treated patients by 16 weeks in a double-blind and randomized phase 4 study.

Oligoarticular PsA can significantly affect quality of life even though few joints are affected, and there’s a lack of relevant clinical data to guide treatment, said rheumatologist Philip J. Mease, MD, of the University of Washington and Swedish Medical Center, Seattle, who reported the results in a presentation at the annual meeting of the American College of Rheumatology.

The findings of the study, called FOREMOST, support the use of the drug in mild PsA, Alexis Ogdie, MD, director of the Penn Psoriatic Arthritis Clinic and the Penn Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia, said in an interview. Dr. Ogdie, who was not involved with the research, noted that rheumatologists commonly prescribe apremilast for mild PsA, although previous research has focused on severe PsA cases.

By 16 weeks, 33.9% of 203 who received apremilast and 16% of 105 who received placebo (difference, 18.5%; 95% confidence interval, 8.9-28.1; P = .0008) met the trial’s primary outcome, a modified version of minimal disease activity score (MDA-Joints), which required attainment of 1 or fewer swollen and/or tender joints plus three of five additional criteria (psoriasis body surface area of 3% or less, a patient pain visual analog scale assessment of 15 mm or less out of 0-100 mm, a patient global assessment of 20 mm or less out of 0-100 mm, a Health Assessment Questionnaire-Disability Index score of 0.5 or less, and a Leeds Enthesitis Index score of 1 or less). The primary analysis was conducted only in joints affected at baseline.

The researchers recruited patients with 2-4 swollen and/or tender joints out of a total of 66-68 joints assessed; most patients (87%) randomized in the study had 4 or fewer active joints at baseline. The patients had a mean age of 50.9. The mean duration of PsA was 9.9 months, and 39.9% of patients were taking a conventional disease-modifying antirheumatic drug.

In a clinically important outcome, the percentage who had a patient-reported pain response improvement defined as “significant” reached 31.4% with placebo, compared with 48.8% for apremilast (difference, 17.7%; 95% CI, 6.0-29.4; P = .0044), and the percentage who reached a patient-reported pain response defined as “major” totaled 19.1% for placebo vs. 41.3% for apremilast (difference, 22.3%; 95% CI, 11.7-32.9; P = .002).

In an exploratory analysis of all joints, the percentages meeting MDA-Joints criteria for response were 7.9% with placebo and 21.3% with apremilast (difference, 13.6%; 95% CI, 5.9-21.4; P = .0028. Focusing on this exploratory analysis, Dr. Ogdie noted that examination of all joints is “more consistent” with the understanding of disease activity than only looking at the initial joints that had disease activity.

A post-hoc analysis among subjects with 2-4 affected joints found rates similar to the primary endpoint analysis: MDA-Joints response rates were reached by 34.4% of those who took apremilast and by 17.2% of those who took placebo.

When asked about the relatively low response rate for apremilast, Dr. Ogdie said the drug is “a really mild medication, which is why it belongs in the mild disease population. That’s balanced by the fact that it has a pretty good safety profile,” especially compared with the alternative of methotrexate, she said.

Almost all patients can tolerate apremilast, she said, although they may experience nausea or diarrhea. (The study found that adverse events were as expected for apremilast, and the drug was well tolerated.) Blood labs aren’t necessary, she added, as they are in patients taking methotrexate.

As for cost, apremilast is a highly expensive drug, especially when compared to methotrexate, which costs pennies per tablet at some pharmacies. Amgen, the manufacturer of apremilast, lists the price as $4,600 a month. Still, insurers generally cover apremilast, Dr. Ogdie said.

The study was sponsored by Amgen. Dr. Mease reported financial relationships with many pharmaceutical companies, including Amgen. Many other coauthors reported financial relationships with Amgen and other pharmaceutical companies or were employees of Amgen. Dr. Ogdie reported having multiple consulting relationships with pharmaceutical companies, including Amgen, and receiving grant funding from multiple companies as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, and Forward Databank.

SAN DIEGO – Patients with early oligoarticular psoriatic arthritis (PsA) who took apremilast (Otezla) had more than double the response rate of placebo-treated patients by 16 weeks in a double-blind and randomized phase 4 study.

Oligoarticular PsA can significantly affect quality of life even though few joints are affected, and there’s a lack of relevant clinical data to guide treatment, said rheumatologist Philip J. Mease, MD, of the University of Washington and Swedish Medical Center, Seattle, who reported the results in a presentation at the annual meeting of the American College of Rheumatology.

The findings of the study, called FOREMOST, support the use of the drug in mild PsA, Alexis Ogdie, MD, director of the Penn Psoriatic Arthritis Clinic and the Penn Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia, said in an interview. Dr. Ogdie, who was not involved with the research, noted that rheumatologists commonly prescribe apremilast for mild PsA, although previous research has focused on severe PsA cases.

By 16 weeks, 33.9% of 203 who received apremilast and 16% of 105 who received placebo (difference, 18.5%; 95% confidence interval, 8.9-28.1; P = .0008) met the trial’s primary outcome, a modified version of minimal disease activity score (MDA-Joints), which required attainment of 1 or fewer swollen and/or tender joints plus three of five additional criteria (psoriasis body surface area of 3% or less, a patient pain visual analog scale assessment of 15 mm or less out of 0-100 mm, a patient global assessment of 20 mm or less out of 0-100 mm, a Health Assessment Questionnaire-Disability Index score of 0.5 or less, and a Leeds Enthesitis Index score of 1 or less). The primary analysis was conducted only in joints affected at baseline.

The researchers recruited patients with 2-4 swollen and/or tender joints out of a total of 66-68 joints assessed; most patients (87%) randomized in the study had 4 or fewer active joints at baseline. The patients had a mean age of 50.9. The mean duration of PsA was 9.9 months, and 39.9% of patients were taking a conventional disease-modifying antirheumatic drug.

In a clinically important outcome, the percentage who had a patient-reported pain response improvement defined as “significant” reached 31.4% with placebo, compared with 48.8% for apremilast (difference, 17.7%; 95% CI, 6.0-29.4; P = .0044), and the percentage who reached a patient-reported pain response defined as “major” totaled 19.1% for placebo vs. 41.3% for apremilast (difference, 22.3%; 95% CI, 11.7-32.9; P = .002).

In an exploratory analysis of all joints, the percentages meeting MDA-Joints criteria for response were 7.9% with placebo and 21.3% with apremilast (difference, 13.6%; 95% CI, 5.9-21.4; P = .0028. Focusing on this exploratory analysis, Dr. Ogdie noted that examination of all joints is “more consistent” with the understanding of disease activity than only looking at the initial joints that had disease activity.

A post-hoc analysis among subjects with 2-4 affected joints found rates similar to the primary endpoint analysis: MDA-Joints response rates were reached by 34.4% of those who took apremilast and by 17.2% of those who took placebo.

When asked about the relatively low response rate for apremilast, Dr. Ogdie said the drug is “a really mild medication, which is why it belongs in the mild disease population. That’s balanced by the fact that it has a pretty good safety profile,” especially compared with the alternative of methotrexate, she said.

Almost all patients can tolerate apremilast, she said, although they may experience nausea or diarrhea. (The study found that adverse events were as expected for apremilast, and the drug was well tolerated.) Blood labs aren’t necessary, she added, as they are in patients taking methotrexate.

As for cost, apremilast is a highly expensive drug, especially when compared to methotrexate, which costs pennies per tablet at some pharmacies. Amgen, the manufacturer of apremilast, lists the price as $4,600 a month. Still, insurers generally cover apremilast, Dr. Ogdie said.

The study was sponsored by Amgen. Dr. Mease reported financial relationships with many pharmaceutical companies, including Amgen. Many other coauthors reported financial relationships with Amgen and other pharmaceutical companies or were employees of Amgen. Dr. Ogdie reported having multiple consulting relationships with pharmaceutical companies, including Amgen, and receiving grant funding from multiple companies as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, and Forward Databank.

SAN DIEGO – Patients with early oligoarticular psoriatic arthritis (PsA) who took apremilast (Otezla) had more than double the response rate of placebo-treated patients by 16 weeks in a double-blind and randomized phase 4 study.

Oligoarticular PsA can significantly affect quality of life even though few joints are affected, and there’s a lack of relevant clinical data to guide treatment, said rheumatologist Philip J. Mease, MD, of the University of Washington and Swedish Medical Center, Seattle, who reported the results in a presentation at the annual meeting of the American College of Rheumatology.

The findings of the study, called FOREMOST, support the use of the drug in mild PsA, Alexis Ogdie, MD, director of the Penn Psoriatic Arthritis Clinic and the Penn Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, Philadelphia, said in an interview. Dr. Ogdie, who was not involved with the research, noted that rheumatologists commonly prescribe apremilast for mild PsA, although previous research has focused on severe PsA cases.

By 16 weeks, 33.9% of 203 who received apremilast and 16% of 105 who received placebo (difference, 18.5%; 95% confidence interval, 8.9-28.1; P = .0008) met the trial’s primary outcome, a modified version of minimal disease activity score (MDA-Joints), which required attainment of 1 or fewer swollen and/or tender joints plus three of five additional criteria (psoriasis body surface area of 3% or less, a patient pain visual analog scale assessment of 15 mm or less out of 0-100 mm, a patient global assessment of 20 mm or less out of 0-100 mm, a Health Assessment Questionnaire-Disability Index score of 0.5 or less, and a Leeds Enthesitis Index score of 1 or less). The primary analysis was conducted only in joints affected at baseline.

The researchers recruited patients with 2-4 swollen and/or tender joints out of a total of 66-68 joints assessed; most patients (87%) randomized in the study had 4 or fewer active joints at baseline. The patients had a mean age of 50.9. The mean duration of PsA was 9.9 months, and 39.9% of patients were taking a conventional disease-modifying antirheumatic drug.

In a clinically important outcome, the percentage who had a patient-reported pain response improvement defined as “significant” reached 31.4% with placebo, compared with 48.8% for apremilast (difference, 17.7%; 95% CI, 6.0-29.4; P = .0044), and the percentage who reached a patient-reported pain response defined as “major” totaled 19.1% for placebo vs. 41.3% for apremilast (difference, 22.3%; 95% CI, 11.7-32.9; P = .002).

In an exploratory analysis of all joints, the percentages meeting MDA-Joints criteria for response were 7.9% with placebo and 21.3% with apremilast (difference, 13.6%; 95% CI, 5.9-21.4; P = .0028. Focusing on this exploratory analysis, Dr. Ogdie noted that examination of all joints is “more consistent” with the understanding of disease activity than only looking at the initial joints that had disease activity.

A post-hoc analysis among subjects with 2-4 affected joints found rates similar to the primary endpoint analysis: MDA-Joints response rates were reached by 34.4% of those who took apremilast and by 17.2% of those who took placebo.

When asked about the relatively low response rate for apremilast, Dr. Ogdie said the drug is “a really mild medication, which is why it belongs in the mild disease population. That’s balanced by the fact that it has a pretty good safety profile,” especially compared with the alternative of methotrexate, she said.

Almost all patients can tolerate apremilast, she said, although they may experience nausea or diarrhea. (The study found that adverse events were as expected for apremilast, and the drug was well tolerated.) Blood labs aren’t necessary, she added, as they are in patients taking methotrexate.

As for cost, apremilast is a highly expensive drug, especially when compared to methotrexate, which costs pennies per tablet at some pharmacies. Amgen, the manufacturer of apremilast, lists the price as $4,600 a month. Still, insurers generally cover apremilast, Dr. Ogdie said.

The study was sponsored by Amgen. Dr. Mease reported financial relationships with many pharmaceutical companies, including Amgen. Many other coauthors reported financial relationships with Amgen and other pharmaceutical companies or were employees of Amgen. Dr. Ogdie reported having multiple consulting relationships with pharmaceutical companies, including Amgen, and receiving grant funding from multiple companies as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, and Forward Databank.

Key clinical point: In women with locally advanced breast cancer (LABC) who received neoadjuvant treatment (NAT) followed by breast surgery, the type of breast surgery, pathological complete response (pCR), body mass index (BMI), and pretreatment stage of tumors were the significant predictors of survival outcomes.

Major finding: Overall survival was significantly improved in patients with LABC who did vs did not achieve pCR (odds ratio [OR] 0.42; P = .008). However, it was much worsened in patients who underwent mastectomy vs breast-conserving surgery (BCS; OR 1.678; P = .024), had higher vs lower BMI (OR 1.031; P = .017), and had stage IIIB or IIIC vs IIB tumors (OR 2.450; P < .001).

Study details: Findings are from a retrospective cohort study including 530 patients with LABC, of which 24.6% of patients underwent BCS after receiving NAT.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nobrega GB et al. Locally advanced breast cancer: Breast-conserving surgery and other factors linked to overall survival after neoadjuvant treatment. Front Oncol. 2023;13:1293288 (Nov 6). doi: 10.3389/fonc.2023.1293288

Key clinical point: In women with locally advanced breast cancer (LABC) who received neoadjuvant treatment (NAT) followed by breast surgery, the type of breast surgery, pathological complete response (pCR), body mass index (BMI), and pretreatment stage of tumors were the significant predictors of survival outcomes.

Major finding: Overall survival was significantly improved in patients with LABC who did vs did not achieve pCR (odds ratio [OR] 0.42; P = .008). However, it was much worsened in patients who underwent mastectomy vs breast-conserving surgery (BCS; OR 1.678; P = .024), had higher vs lower BMI (OR 1.031; P = .017), and had stage IIIB or IIIC vs IIB tumors (OR 2.450; P < .001).

Study details: Findings are from a retrospective cohort study including 530 patients with LABC, of which 24.6% of patients underwent BCS after receiving NAT.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nobrega GB et al. Locally advanced breast cancer: Breast-conserving surgery and other factors linked to overall survival after neoadjuvant treatment. Front Oncol. 2023;13:1293288 (Nov 6). doi: 10.3389/fonc.2023.1293288

Key clinical point: In women with locally advanced breast cancer (LABC) who received neoadjuvant treatment (NAT) followed by breast surgery, the type of breast surgery, pathological complete response (pCR), body mass index (BMI), and pretreatment stage of tumors were the significant predictors of survival outcomes.

Major finding: Overall survival was significantly improved in patients with LABC who did vs did not achieve pCR (odds ratio [OR] 0.42; P = .008). However, it was much worsened in patients who underwent mastectomy vs breast-conserving surgery (BCS; OR 1.678; P = .024), had higher vs lower BMI (OR 1.031; P = .017), and had stage IIIB or IIIC vs IIB tumors (OR 2.450; P < .001).

Study details: Findings are from a retrospective cohort study including 530 patients with LABC, of which 24.6% of patients underwent BCS after receiving NAT.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nobrega GB et al. Locally advanced breast cancer: Breast-conserving surgery and other factors linked to overall survival after neoadjuvant treatment. Front Oncol. 2023;13:1293288 (Nov 6). doi: 10.3389/fonc.2023.1293288

Key clinical point: Patients with breast cancer (BC) who underwent post-mastectomy breast reconstruction followed by post-mastectomy radiotherapy (PMRT) had an increased risk for postoperative complications, such as infections and contractures, than those who did not receive PMRT.

Major finding: Patients who did vs did not receive PMRT had a significantly higher risk for postoperative wound infections (odds ratio [OR] 1.95; P = .003) and skin contractures (OR 7.24; P = .005).

Study details: Findings are from a meta-analysis of 11 studies including 2288 patients with BC who underwent breast reconstruction, of which 516 patients received PMRT after breast reconstruction.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Huang N, Lu L, et al. Effect of radiation therapy during surgery on postoperative wound complications after breast reconstruction in patients with breast cancer: A meta-analysis. Int Wound J. 2023 (Oct 31). doi: 10.1111/iwj.14473

Key clinical point: Patients with breast cancer (BC) who underwent post-mastectomy breast reconstruction followed by post-mastectomy radiotherapy (PMRT) had an increased risk for postoperative complications, such as infections and contractures, than those who did not receive PMRT.

Major finding: Patients who did vs did not receive PMRT had a significantly higher risk for postoperative wound infections (odds ratio [OR] 1.95; P = .003) and skin contractures (OR 7.24; P = .005).

Study details: Findings are from a meta-analysis of 11 studies including 2288 patients with BC who underwent breast reconstruction, of which 516 patients received PMRT after breast reconstruction.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Huang N, Lu L, et al. Effect of radiation therapy during surgery on postoperative wound complications after breast reconstruction in patients with breast cancer: A meta-analysis. Int Wound J. 2023 (Oct 31). doi: 10.1111/iwj.14473

Key clinical point: Patients with breast cancer (BC) who underwent post-mastectomy breast reconstruction followed by post-mastectomy radiotherapy (PMRT) had an increased risk for postoperative complications, such as infections and contractures, than those who did not receive PMRT.

Major finding: Patients who did vs did not receive PMRT had a significantly higher risk for postoperative wound infections (odds ratio [OR] 1.95; P = .003) and skin contractures (OR 7.24; P = .005).

Study details: Findings are from a meta-analysis of 11 studies including 2288 patients with BC who underwent breast reconstruction, of which 516 patients received PMRT after breast reconstruction.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Huang N, Lu L, et al. Effect of radiation therapy during surgery on postoperative wound complications after breast reconstruction in patients with breast cancer: A meta-analysis. Int Wound J. 2023 (Oct 31). doi: 10.1111/iwj.14473

Key clinical point: Robotic nipple-sparing mastectomy (RNSM) may soon become a viable option for breast cancer (BC) surgery as it is associated with lower postoperative complication rates than conventional NSM (CNSM).

Major finding: RNSM vs CNSM was associated with a significantly lower rate of nipple necrosis, a major postoperative complication (odds ratio 0.54; P = .03), and intraoperative blood loss (mean difference [MD] −53.18 mL; P < .00001), but a significantly higher operating time (MD +58.81 min; P < .001).

Study details: Findings are from a meta-analysis of seven studies including 1674 women with BC who underwent RNSM (50.9%) or CNSM (49.1%).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nessa A et al. Postoperative complications and surgical outcomes of robotic versus conventional nipple-sparing mastectomy in breast cancer: Meta-analysis. Br J Surg. 2023 (Oct 27). doi: 10.1093/bjs/znad336

Key clinical point: Robotic nipple-sparing mastectomy (RNSM) may soon become a viable option for breast cancer (BC) surgery as it is associated with lower postoperative complication rates than conventional NSM (CNSM).

Major finding: RNSM vs CNSM was associated with a significantly lower rate of nipple necrosis, a major postoperative complication (odds ratio 0.54; P = .03), and intraoperative blood loss (mean difference [MD] −53.18 mL; P < .00001), but a significantly higher operating time (MD +58.81 min; P < .001).

Study details: Findings are from a meta-analysis of seven studies including 1674 women with BC who underwent RNSM (50.9%) or CNSM (49.1%).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nessa A et al. Postoperative complications and surgical outcomes of robotic versus conventional nipple-sparing mastectomy in breast cancer: Meta-analysis. Br J Surg. 2023 (Oct 27). doi: 10.1093/bjs/znad336

Key clinical point: Robotic nipple-sparing mastectomy (RNSM) may soon become a viable option for breast cancer (BC) surgery as it is associated with lower postoperative complication rates than conventional NSM (CNSM).

Major finding: RNSM vs CNSM was associated with a significantly lower rate of nipple necrosis, a major postoperative complication (odds ratio 0.54; P = .03), and intraoperative blood loss (mean difference [MD] −53.18 mL; P < .00001), but a significantly higher operating time (MD +58.81 min; P < .001).

Study details: Findings are from a meta-analysis of seven studies including 1674 women with BC who underwent RNSM (50.9%) or CNSM (49.1%).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Nessa A et al. Postoperative complications and surgical outcomes of robotic versus conventional nipple-sparing mastectomy in breast cancer: Meta-analysis. Br J Surg. 2023 (Oct 27). doi: 10.1093/bjs/znad336

Key clinical point: Adjuvant chemotherapy significantly improved the overall survival (OS) outcomes in patients with small-size (T1b and T1c) node-negative triple-negative breast cancer (TNBC).

Major finding: Adjuvant chemotherapy led to significantly better OS outcomes in patients with T1b TNBC (adjusted hazard ratio [aHR] 0.52; P < .001) and improved both OS (aHR 0.54; P < .001) and breast cancer-specific survival (aHR 0.79; P = .043) in those with T1c TNBC.

Study details: This retrospective study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER) database and included 11,510 women with T1b (n = 3388) or T1c (n = 8122) node-negative TNBC, of whom 8029 patients received adjuvant chemotherapy.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Carbajal-Ochoa W et al. Benefit of adjuvant chemotherapy in lymph node-negative, T1b and T1c triple-negative breast cancer. Breast Cancer Res Treat. 2023 (Oct 13). doi: 10.1007/s10549-023-07132-6

Key clinical point: Adjuvant chemotherapy significantly improved the overall survival (OS) outcomes in patients with small-size (T1b and T1c) node-negative triple-negative breast cancer (TNBC).

Major finding: Adjuvant chemotherapy led to significantly better OS outcomes in patients with T1b TNBC (adjusted hazard ratio [aHR] 0.52; P < .001) and improved both OS (aHR 0.54; P < .001) and breast cancer-specific survival (aHR 0.79; P = .043) in those with T1c TNBC.

Study details: This retrospective study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER) database and included 11,510 women with T1b (n = 3388) or T1c (n = 8122) node-negative TNBC, of whom 8029 patients received adjuvant chemotherapy.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Carbajal-Ochoa W et al. Benefit of adjuvant chemotherapy in lymph node-negative, T1b and T1c triple-negative breast cancer. Breast Cancer Res Treat. 2023 (Oct 13). doi: 10.1007/s10549-023-07132-6

Key clinical point: Adjuvant chemotherapy significantly improved the overall survival (OS) outcomes in patients with small-size (T1b and T1c) node-negative triple-negative breast cancer (TNBC).

Major finding: Adjuvant chemotherapy led to significantly better OS outcomes in patients with T1b TNBC (adjusted hazard ratio [aHR] 0.52; P < .001) and improved both OS (aHR 0.54; P < .001) and breast cancer-specific survival (aHR 0.79; P = .043) in those with T1c TNBC.

Study details: This retrospective study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER) database and included 11,510 women with T1b (n = 3388) or T1c (n = 8122) node-negative TNBC, of whom 8029 patients received adjuvant chemotherapy.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Carbajal-Ochoa W et al. Benefit of adjuvant chemotherapy in lymph node-negative, T1b and T1c triple-negative breast cancer. Breast Cancer Res Treat. 2023 (Oct 13). doi: 10.1007/s10549-023-07132-6