Anticipating Food and Drug Administration approval of at least one investigational device for renal denervation (RDN) as a treatment for hypertension (HTN) refractory to medical therapies, the Society for Cardiovascular Angiography and Interventions is asking its members and the public to provide input on a draft position statement to guide use of the procedure.

The draft addresses appropriate patient selection, best practices for procedural techniques, measures for operator competence, recommendations for operator and staff training, and guidance for hospitals and centers that want to adopt RDN. SCAI is requesting feedback by June 14.

“With the anticipated FDA approval of renal denervation, there will be a need for SCAI to formulate an official position around clinical competence and training standards, best practices, and institutional and operator requirements for RDN,” Herbert D. Aronow, MD, MPH, chair of the statement writing committee, said in an interview.

RDN is an endoscopic procedure that disrupts the sympathetic nerves near the renal arteries. A number of studies, including sham-controlled, randomized trials, have shown that RDN can achieve short-term reductions in blood pressure for patients for whom HTN medications don’t work. Two devices are awaiting FDA premarket approval: the Paradise uRDN system, by ReCor Medical; and the Symplicity Spyral device, by Medtronic.

However, the trajectory of RDN has been uneven, said Dr. Aronow, president of the Society for Vascular Medicine and medical director for heart and vascular services and Benson Ford Chair in cardiology at Henry Ford Health, Detroit.

“Despite supportive early animal and human data, the first sham-controlled randomized trial of RDN was negative on its primary endpoint,” he said. “Modifications to patient inclusion/exclusion criteria, refinements in denervation technology and protocols, and selection of more appropriate study endpoints resulted in a series of positive randomized, sham-controlled trials. These second-generation trials found that RDN, when compared with sham therapy, substantially reduced ambulatory and office blood pressures.”

The draft is available for review at the SCAI website. Comments may be submitted via a link to a questionnaire.

“Through the open comment process, we are hoping to gain broad perspective from stakeholders, including clinicians, hospitals, payers, professional societies, industry and patients,” Dr. Aronow said. “By incorporating this feedback, we hope to enhance the quality of the document before we submit it for publication.”

The bulk of the SCAI draft position statement is devoted to patient selection and procedural and technical considerations. “We believe it will serve as a road map for the successful launch of RDN programs around the United States,” Dr. Aronow said.
 

Patient selection considerations

The draft statement notes that RDN for all patients with uncontrolled HTN “would not currently be practical.” The average age of patients for whom RDN showed effectiveness in the cited clinical trials was less than 60 years. The effectiveness of RDN for patients in whom arterial stiffness is a primary driver of HTN “is less certain.”

Patients who may benefit most from RDN are those with limited medical treatment options. Initially, RDN was tried on patients who had continued to experience resistant HTN despite taking three or more medications, including a diuretic, the statement noted. But even nonadherent patients may derive some potential benefit from RDN.

The statement also added that RDN isn’t a panacea; about one-third of trial patients didn’t respond to the procedure. The most reliable predictor of response may be higher levels of baseline systolic blood pressure, otherwise known as Wilder’s principle. The statement listed other potential markers of success, including higher nocturnal blood pressure and wider swings in nocturnal blood pressure.
 

Procedural and technical considerations

The statement also provided direction on a protocol for RDN procedures. The preprocedure evaluation should include noninvasive imaging to rule out disqualifying secondary causes of HTN, such as renal artery stenosis or fibromuscular dysplasia.

Patient characteristics should drive the selection of imaging modality, and availability as well as local expertise should be taken into account. The statement gave CT angiography or magnetic resonance angiography the edge over duplex ultrasound.

The statement also noted a number of anatomic considerations, citing preclinical analyses that “consistently reinforce” circumferential, perivascular RDN to ablate the renal nerves. In planning the procedure, consideration should be given to accessory renal arteries.

Additionally, operators should have training in obtaining access, and they should be familiar with different catheters and console devices as well as troubleshooting.
 

Training, competency, and institutional requirements

Interventional cardiologists who want to perform RDN should demonstrate proficiency in a number of specific skill sets germane to the procedure, from arterial vascular access and hemostasis to recognizing and treating potential renovascular complications.

For institutions that want to offer RDN, the statement offered a number of requirements. One is to designate a primary physician stakeholder who’s well versed in HTN management to oversee the long-term management of RDN patients.

The institution must have a dedicated HTN program and a multidisciplinary team to manage treated patients. Requirements for RDN referral centers range from operators experienced with FDA-approved RDN devices to an infrastructure that includes CT or MR angiography to identify appropriate candidates.

“Renal denervation has been a long time coming, and it’s a great example of how academicians, clinicians and industry leaders can partner to move the cardiovascular field forward, addressing a major public health issue for which alternative solutions are greatly needed,” Dr. Aronow said.

Dr. Aronow has served as an unpaid council member for Medtronic and as a paid moderator for ReCor.

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

Anticipating Food and Drug Administration approval of at least one investigational device for renal denervation (RDN) as a treatment for hypertension (HTN) refractory to medical therapies, the Society for Cardiovascular Angiography and Interventions is asking its members and the public to provide input on a draft position statement to guide use of the procedure.

The draft addresses appropriate patient selection, best practices for procedural techniques, measures for operator competence, recommendations for operator and staff training, and guidance for hospitals and centers that want to adopt RDN. SCAI is requesting feedback by June 14.

“With the anticipated FDA approval of renal denervation, there will be a need for SCAI to formulate an official position around clinical competence and training standards, best practices, and institutional and operator requirements for RDN,” Herbert D. Aronow, MD, MPH, chair of the statement writing committee, said in an interview.

RDN is an endoscopic procedure that disrupts the sympathetic nerves near the renal arteries. A number of studies, including sham-controlled, randomized trials, have shown that RDN can achieve short-term reductions in blood pressure for patients for whom HTN medications don’t work. Two devices are awaiting FDA premarket approval: the Paradise uRDN system, by ReCor Medical; and the Symplicity Spyral device, by Medtronic.

However, the trajectory of RDN has been uneven, said Dr. Aronow, president of the Society for Vascular Medicine and medical director for heart and vascular services and Benson Ford Chair in cardiology at Henry Ford Health, Detroit.

“Despite supportive early animal and human data, the first sham-controlled randomized trial of RDN was negative on its primary endpoint,” he said. “Modifications to patient inclusion/exclusion criteria, refinements in denervation technology and protocols, and selection of more appropriate study endpoints resulted in a series of positive randomized, sham-controlled trials. These second-generation trials found that RDN, when compared with sham therapy, substantially reduced ambulatory and office blood pressures.”

The draft is available for review at the SCAI website. Comments may be submitted via a link to a questionnaire.

“Through the open comment process, we are hoping to gain broad perspective from stakeholders, including clinicians, hospitals, payers, professional societies, industry and patients,” Dr. Aronow said. “By incorporating this feedback, we hope to enhance the quality of the document before we submit it for publication.”

The bulk of the SCAI draft position statement is devoted to patient selection and procedural and technical considerations. “We believe it will serve as a road map for the successful launch of RDN programs around the United States,” Dr. Aronow said.
 

Patient selection considerations

The draft statement notes that RDN for all patients with uncontrolled HTN “would not currently be practical.” The average age of patients for whom RDN showed effectiveness in the cited clinical trials was less than 60 years. The effectiveness of RDN for patients in whom arterial stiffness is a primary driver of HTN “is less certain.”

Patients who may benefit most from RDN are those with limited medical treatment options. Initially, RDN was tried on patients who had continued to experience resistant HTN despite taking three or more medications, including a diuretic, the statement noted. But even nonadherent patients may derive some potential benefit from RDN.

The statement also added that RDN isn’t a panacea; about one-third of trial patients didn’t respond to the procedure. The most reliable predictor of response may be higher levels of baseline systolic blood pressure, otherwise known as Wilder’s principle. The statement listed other potential markers of success, including higher nocturnal blood pressure and wider swings in nocturnal blood pressure.
 

Procedural and technical considerations

The statement also provided direction on a protocol for RDN procedures. The preprocedure evaluation should include noninvasive imaging to rule out disqualifying secondary causes of HTN, such as renal artery stenosis or fibromuscular dysplasia.

Patient characteristics should drive the selection of imaging modality, and availability as well as local expertise should be taken into account. The statement gave CT angiography or magnetic resonance angiography the edge over duplex ultrasound.

The statement also noted a number of anatomic considerations, citing preclinical analyses that “consistently reinforce” circumferential, perivascular RDN to ablate the renal nerves. In planning the procedure, consideration should be given to accessory renal arteries.

Additionally, operators should have training in obtaining access, and they should be familiar with different catheters and console devices as well as troubleshooting.
 

Training, competency, and institutional requirements

Interventional cardiologists who want to perform RDN should demonstrate proficiency in a number of specific skill sets germane to the procedure, from arterial vascular access and hemostasis to recognizing and treating potential renovascular complications.

For institutions that want to offer RDN, the statement offered a number of requirements. One is to designate a primary physician stakeholder who’s well versed in HTN management to oversee the long-term management of RDN patients.

The institution must have a dedicated HTN program and a multidisciplinary team to manage treated patients. Requirements for RDN referral centers range from operators experienced with FDA-approved RDN devices to an infrastructure that includes CT or MR angiography to identify appropriate candidates.

“Renal denervation has been a long time coming, and it’s a great example of how academicians, clinicians and industry leaders can partner to move the cardiovascular field forward, addressing a major public health issue for which alternative solutions are greatly needed,” Dr. Aronow said.

Dr. Aronow has served as an unpaid council member for Medtronic and as a paid moderator for ReCor.

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

Anticipating Food and Drug Administration approval of at least one investigational device for renal denervation (RDN) as a treatment for hypertension (HTN) refractory to medical therapies, the Society for Cardiovascular Angiography and Interventions is asking its members and the public to provide input on a draft position statement to guide use of the procedure.

The draft addresses appropriate patient selection, best practices for procedural techniques, measures for operator competence, recommendations for operator and staff training, and guidance for hospitals and centers that want to adopt RDN. SCAI is requesting feedback by June 14.

“With the anticipated FDA approval of renal denervation, there will be a need for SCAI to formulate an official position around clinical competence and training standards, best practices, and institutional and operator requirements for RDN,” Herbert D. Aronow, MD, MPH, chair of the statement writing committee, said in an interview.

RDN is an endoscopic procedure that disrupts the sympathetic nerves near the renal arteries. A number of studies, including sham-controlled, randomized trials, have shown that RDN can achieve short-term reductions in blood pressure for patients for whom HTN medications don’t work. Two devices are awaiting FDA premarket approval: the Paradise uRDN system, by ReCor Medical; and the Symplicity Spyral device, by Medtronic.

However, the trajectory of RDN has been uneven, said Dr. Aronow, president of the Society for Vascular Medicine and medical director for heart and vascular services and Benson Ford Chair in cardiology at Henry Ford Health, Detroit.

“Despite supportive early animal and human data, the first sham-controlled randomized trial of RDN was negative on its primary endpoint,” he said. “Modifications to patient inclusion/exclusion criteria, refinements in denervation technology and protocols, and selection of more appropriate study endpoints resulted in a series of positive randomized, sham-controlled trials. These second-generation trials found that RDN, when compared with sham therapy, substantially reduced ambulatory and office blood pressures.”

The draft is available for review at the SCAI website. Comments may be submitted via a link to a questionnaire.

“Through the open comment process, we are hoping to gain broad perspective from stakeholders, including clinicians, hospitals, payers, professional societies, industry and patients,” Dr. Aronow said. “By incorporating this feedback, we hope to enhance the quality of the document before we submit it for publication.”

The bulk of the SCAI draft position statement is devoted to patient selection and procedural and technical considerations. “We believe it will serve as a road map for the successful launch of RDN programs around the United States,” Dr. Aronow said.
 

Patient selection considerations

The draft statement notes that RDN for all patients with uncontrolled HTN “would not currently be practical.” The average age of patients for whom RDN showed effectiveness in the cited clinical trials was less than 60 years. The effectiveness of RDN for patients in whom arterial stiffness is a primary driver of HTN “is less certain.”

Patients who may benefit most from RDN are those with limited medical treatment options. Initially, RDN was tried on patients who had continued to experience resistant HTN despite taking three or more medications, including a diuretic, the statement noted. But even nonadherent patients may derive some potential benefit from RDN.

The statement also added that RDN isn’t a panacea; about one-third of trial patients didn’t respond to the procedure. The most reliable predictor of response may be higher levels of baseline systolic blood pressure, otherwise known as Wilder’s principle. The statement listed other potential markers of success, including higher nocturnal blood pressure and wider swings in nocturnal blood pressure.
 

Procedural and technical considerations

The statement also provided direction on a protocol for RDN procedures. The preprocedure evaluation should include noninvasive imaging to rule out disqualifying secondary causes of HTN, such as renal artery stenosis or fibromuscular dysplasia.

Patient characteristics should drive the selection of imaging modality, and availability as well as local expertise should be taken into account. The statement gave CT angiography or magnetic resonance angiography the edge over duplex ultrasound.

The statement also noted a number of anatomic considerations, citing preclinical analyses that “consistently reinforce” circumferential, perivascular RDN to ablate the renal nerves. In planning the procedure, consideration should be given to accessory renal arteries.

Additionally, operators should have training in obtaining access, and they should be familiar with different catheters and console devices as well as troubleshooting.
 

Training, competency, and institutional requirements

Interventional cardiologists who want to perform RDN should demonstrate proficiency in a number of specific skill sets germane to the procedure, from arterial vascular access and hemostasis to recognizing and treating potential renovascular complications.

For institutions that want to offer RDN, the statement offered a number of requirements. One is to designate a primary physician stakeholder who’s well versed in HTN management to oversee the long-term management of RDN patients.

The institution must have a dedicated HTN program and a multidisciplinary team to manage treated patients. Requirements for RDN referral centers range from operators experienced with FDA-approved RDN devices to an infrastructure that includes CT or MR angiography to identify appropriate candidates.

“Renal denervation has been a long time coming, and it’s a great example of how academicians, clinicians and industry leaders can partner to move the cardiovascular field forward, addressing a major public health issue for which alternative solutions are greatly needed,” Dr. Aronow said.

Dr. Aronow has served as an unpaid council member for Medtronic and as a paid moderator for ReCor.

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

The US Department of Health and Human Services (HHS) Ending the HIV Epidemic framework aims to decrease HIV infections in the United States by 90% before 2030.¹ Achieving this goal requires identifying persons at high risk for HIV and ensuring timely and efficient access to HIV preexposure prophylaxis (PrEP).^2-5 However, despite its commercial availability since 2012, community uptake of PrEP is low.⁶ In 2019, < 25% of Americans who could benefit from PrEP were using this preventive therapy.⁷ Poor uptake of PrEP has also been documented among veterans and US military service members. National data on men in the military and men who have sex with men (MSM) in the military suggest that about 12,000 service members are eligible for PrEP; however, only 2000 service members and their beneficiaries accessed PrEP in February 2017.⁸

A review of health records of US military service members conducted from 2014 to 2016 indicated that most patients who received PrEP did not receive recommended monitoring in accordance with the Centers for Disease Control and Prevention (CDC) guidelines. Furthermore, 16% of these individuals did not have HIV testing within 14 days of initiating PrEP, and 13% were never evaluated for hepatitis B infection.⁸

Pharmacists are highly accessible health care professionals (HCPs): More than 90% of Americans live within 5 miles of a community pharmacy.⁹ Pharmacists play an integral role within the outpatient health care team and have been responsible for improvements in health care outcomes for a variety of chronic conditions and immunization practices.^10-13 Additionally, community pharmacists have provided vital access to care during the COVID-19 pandemic.¹⁴ The clinical pharmacist practitioner (CPP) is an innovative and advanced role within the Veterans Health Administration (VHA), functioning with a scope of practice and prescribing privileges to provide direct patient care.¹⁵

CPPs are well suited to address the need for increased access, capacity, and timely provision of PrEP, especially in areas where HIV acquisition rates are high or in areas with reduced access to care. We describe a model for a pharmacist-led HIV PrEP program (Pharm-PrEP) to increase access to PrEP. A similar program could be adapted to further expand the use of PrEP in other health care systems and community settings.

Pharm-PrEP Program Description

The Veterans Affairs Greater Los Angeles Healthcare System (VAGLAHCS) provides health care services at 11 locations in southern California and serves > 86,000 veterans. The VAGLAHCS pharmacy staff includes 33 CPPs who practice in more than 9 clinical service lines. HIV PrEP services are available through the infectious diseases (ID) service for veterans wishing to begin or continue PrEP or for those identified as high risk. HIV PrEP consultations are placed by the referring HCP to the ID service for scheduling and evaluation. Prior to implementation of the pharmacist-managed PrEP clinic, 2 ID physician assistants (PAs) were responsible for PrEP evaluation, initiation, and follow-up. Each PA had 1 half-day face-to-face clinic and 1 PA had an additional half-day telehealth clinic. About 100 PrEP patients were followed by the ID group.

In July 2019, through collaboration with the ID service, a pharmacy PrEP clinic was created to increase access for veterans to initiate or continue PrEP. This clinic included 1 ID-trained CPP and 1 postgraduate-year-2 pharmacy resident. The CPP initiates and monitors veterans for HIV PrEP with prescribing privileges under a defined scope of practice.

Awareness of this novel service was raised through in-service training sessions for primary care and women’s health clinics. Referrals are generated directly from primary care practitioners (PCPs) or emergency department (ED) visits and are accepted on a continuing basis. Visits with the CPP are conducted in person or through telehealth services based on patient preference. Direct CPP patient care appointments involve a standardized assessment and discussion of patient HIV transmission risk, a review of social and sexual history, sexual practices and HIV risk, clinical evidence of acute HIV or other sexually transmitted infection (STI) symptoms, follow-up PrEP monitoring requirements, and counseling on appropriate PrEP use. CPPs can order laboratory tests, bone densitometry (DEXA scan), immunizations, PrEP, and STI treatment as required. ID service physicians are available during CPP visits for further assessment or consultation. While initially most visits are conducted in person, follow-up visits by telehealth or video have become predominant; most patients prefer these modalities, citing convenience, flexibility, and the ability to obtain laboratory tests in advance. Use of telephone and video is intended to reduce patient loss to follow-up.

All required baseline laboratory panels for PrEP monitoring are ordered and interpreted by the CPP in accordance with CDC guidelines.¹⁶ These include screening for syphilis, gonorrhea, and chlamydia; fourth-generation antibody-antigen HIV tests; renal function; viral hepatitis; and pregnancy. After reviewing screening results, the CPP will prescribe tenofovir disproxil fumarate/emtricitabine (TDF/FTC) or tenofovir alafenamide/emtricitabine (TAF/FTC) based on individual patient clinical characteristics, US Food and Drug Administration–approved labeling, and VA Pharmacy Benefits Management Criteria for Use. Initial prescriptions are for a 30-day supply with subsequent prescriptions for 90 days (no refills), providing follow-up HIV testing is completed.

Follow-up PrEP visits are scheduled about every 3 months with some overlap to avoid gaps in medication due to late laboratory testing or delayed receipt of mailed medications. The only laboratory testing strictly required each quarter before PrEP renewal is HIV and pregnancy testing. Other screenings, including STIs and renal function are completed at least every 6 months or more frequently, if indicated, based on individual risk factors. Hepatitis C antibody testing is conducted annually if the patient has ongoing risk factors. Treatment of gonorrhea/chlamydia and syphilis for patients with positive test results is also initiated by the CPP, including recommending antimicrobial regimens. Additional interventions conducted as part of the clinic include indicated vaccinations (meningococcal, human papillomavirus, hepatitis A and B), and DEXA scans. Collaboration with ID service attendings and PAs is conducted on an as-needed basis via direct consultation in the colocated clinic or through email or messaging.

Periodic surveillance of a local dashboard of veterans eligible for HIV PrEP is conducted to re-engage veterans in care who may have been lost to follow-up, along with periodic review of a local STI dashboard. These dashboards capture population-based data to identify patients who may benefit from additional STI screenings as well as potential candidates for HIV PrEP. Clinicians can review their patient panel to target individuals who may be due for specific actions. Patients are identified as needing cotesting if they screen positive for ≥ 1 STIs but have not had a concurrent or subsequent full screening panel (gonorrhea, chlamydia, syphilis, and HIV). Cotesting for bacterial STIs and HIV at the time of an encounter has been promoted to expedite STI identification and treatment and limit community transmission. These reports also identify patients who may be potential candidates for HIV PrEP, based on a history of positive screenings, frequent STI testing, recent prescriptions for postexposure prophylaxis (PEP) or encounters with specific International Classification of Diseases codes associated with high-risk practices.

Clinic Quality of Care

From July 2019 to March 2020, 53 veterans were managed by the pharm-PrEP clinic in 98 encounters. Seventy percent of encounters were in-person (Table 1).

Baseline information collected included demographics, documented patient-reported risk factors, fourth-generation HIV screening test results, STI status, viral hepatitis serologies, and renal function test results. Information collected every 3 to 6 months included STI status, fourth-generation HIV screening test results, renal function test results, adherence to therapy, changes in risk factors, and prescription refill data. Additional interventions conducted as part of clinic workflow included DEXA scans, vaccinations, and active prescriptions for condoms.

Baseline Characteristics

Pharm-PrEP clinic patients were predominantly male (94%), and a majority indicated White race with a median age of 38 years (range, 24-80 years).

Veterans referred to the clinic had up to 5 risk factors for PrEP initiation. The most common risk factors were inconsistent condom use (62%), multiple sexual partners of unknown HIV status (62%), MSM (57%), STI history (38%), bisexual partners (25%), and HIV-positive sexual partners (11%). One of the 53 individuals referred for PrEP had no risk factors and did not initiate PrEP. Two individuals declined initiation of PrEP after consultation. Twenty six of 53 veterans at baseline continued their use of PrEP following transfer to clinic CPP management; 24 of 27 veterans not currently using PrEP (89%) started or restarted lapsed PrEP use following CPP consultation.

HIV and STI Screening

No individuals tested positive for HIV at baseline (n = 52) or while on PrEP. PrEP was not renewed for 3 patients that did follow through with HIV testing. The median number of days an HIV test was completed prior to initial PrEP and PrEP renewal was 4 days and < 7 days, respectively, both of which are below the recommended maximal interval of 7 days, according to CDC PrEP guidelines. Some postinitiation HIV testing occurred using a longer interval of 14 days, in accordance with VA National Criteria for Use of PrEP. This modification allowed more flexibility as a majority of PrEP prescriptions are sent to veterans via mail. The CPP reviewing HIV test results was able to expedite the processing and mailing of PrEP prescriptions if deemed appropriate, ie, the HIV test was negative. This approach was not used if a patient had high-risk exposures without PrEP during the time between collection of the HIV test and mailing of the prescription.

STI screening is a vital component of the Pharm-PrEP clinic and helped identify 4 patients with gonorrhea/chlamydia at baseline and 1 with syphilis after initiation of PrEP. All patients were prescribed antibiotics at the screening. Los Angeles County has high rates of STI transmission;thus implementation of clinic processes allowing the CPP to screen for STIs, interpret test results, and treat patients with STIs is vital to limit spread in the community.¹⁷

Selection of PrEP Regimen

The majority of individuals in the cohort received TDF/FTC for PrEP; TAF/FTC was restricted to individuals who had documented renal dysfunction or bone loss (Table 3).

Six DEXA scans were completed by the end of the evaluation period and 2 had abnormal results. One patient discontinued TDF/FTC and reinitiated with TAF/FTC. The other was switched to TAF/FTC 1 month after initiation.

Follow-Up Visits

The median number of visits per patient was 2. The median time between visits was in accordance with recommended follow-up intervals with 35 days between visits 1 and 2, 60 days between visits 2 and 3, and 88 days thereafter. In all, 10 veterans (20%) stopped PrEP: 4 (8%) were lost to follow-up; 3 (6%) had sustained behavior changes decreasing their HIV exposure risk; 2 (4%) were concerned about ADRs; and 1 (2%) moved out of state. Even after including those patients with a decrease in HIV exposure risk who no longer required PrEP, our 20% discontinuation rate was lower than those reported in other studies that showed a wide variation in PrEP discontinuation rates ranging from 33% to 62%.^18-20

Challenges

Some challenges with the implementation of the clinic included logistic and operational barriers, such as developing clinical pathways and managing workflow to facilitate vaccinations or STI treatment for individuals using video or telehealth services, as well as encouraging referrals from PCPs. These challenges were addressed by providing periodic targeted in-service training sessions to primary care teams to increase awareness of the Pharm-PrEP clinic. Collaboration with the ID service and ED allowed implementation of a direct pathway for patients initiated on nonoccupational HIV PEP after a high-risk exposure to be evaluated for transition to HIV PrEP. This PEP-2-PrEP pathway was designed to decrease barriers to follow-up for high-risk individuals who had recently received PEP in the ED. The CPP plays an active, integral role in managing patient care in the PEP-2-PrEP pathway.

Pharmacist-Led PrEP Care

The implementation of the VAGLAHCS Pharm-PrEP clinic demonstrates how CPPs can expand access and manage HIV PrEP with high reliability. Key factors for successfully integrating CPPs as PrEP prescribers include identifying physician champions; using in-services or other training platforms to raise awareness among potential referring HCPs and stimulate referrals; and developing processes to identify high-risk veterans. Also, nontraditional modes of care, such as video or telehealth appointments, can increase access and expand the volume of patient care visits. Such modalities are useful for PrEP management when combined with a well-defined operational process for laboratory specimen collection before appointments. This system is particularly well suited to increasing access to PrEP for patients who live in rural or highly rural areas that are medically underserved or who have difficulty traveling to a clinical facility for an in-person visit.

Although community health care organizations and HCPs face pay barriers not present in the VHA system, several studies have demonstrated feasability of pharmacist-led clinics in private health care systems.^21-24 Havens and colleagues described a PrEP program affilitated with an university that assessed patient satisfaction and pharmacist acceptability with this new service.²² The results of surveys reported high patient satisfaction and pharmacist acceptability.²³ Tung and colleagues described a PrEP clinic located in a community pharmacy with the ability to bill for pharmacist and laboratory services in addition to medication costs.²⁴ These studies, along with our findings, demonstrate that CPPs are well positioned to manage HIV PrEP in the community. Leveraging the skills and experience of CPPs to address poor uptake and access to PrEP should be a central component in achieving the goals of the Ending the HIV Epidemic initiative, given that pharmacists are one of the most accessible groups of HCPs nationally.

Pharmacist prescriptive authority varies across different states and may depend on collaborative practice agreements, statewide protocols, or class-specific prescribing.²⁵ For example, California was among the first states to authorize initiation and prescription of HIV PrEP and PEP by pharmacists in specified amounts after appropriate training.²⁶ Nationwide support for similar policies in the community and within health care systems will be critical to the successful implementation and functioning of pharmacy-led PrEP clinics.

Conclusions

The success of this Pharm-PrEP clinic was largely due to a collaborative, interdisciplinary effort to implement this new clinic process and incorporate the CPP into the general ID outpatient clinic, while allowing flexibility in scheduling and use of different encounter modalities for patients. Deploying pharmacists as PrEP prescribers can help health care systems increase PrEP access and capacity and improve efforts to achieve the goals of the Ending the HIV Epidemic. This type of program can be a model for other health care organizations and systems to implement pharmacy-led PrEP clinics and expand telehealth modalities to deliver PrEP.

Acknowledgments

The infectious diseases service at the Veterans Affairs Greater Los Angeles Healthcare System and the veterans we serve.

The US Department of Health and Human Services (HHS) Ending the HIV Epidemic framework aims to decrease HIV infections in the United States by 90% before 2030.¹ Achieving this goal requires identifying persons at high risk for HIV and ensuring timely and efficient access to HIV preexposure prophylaxis (PrEP).^2-5 However, despite its commercial availability since 2012, community uptake of PrEP is low.⁶ In 2019, < 25% of Americans who could benefit from PrEP were using this preventive therapy.⁷ Poor uptake of PrEP has also been documented among veterans and US military service members. National data on men in the military and men who have sex with men (MSM) in the military suggest that about 12,000 service members are eligible for PrEP; however, only 2000 service members and their beneficiaries accessed PrEP in February 2017.⁸

A review of health records of US military service members conducted from 2014 to 2016 indicated that most patients who received PrEP did not receive recommended monitoring in accordance with the Centers for Disease Control and Prevention (CDC) guidelines. Furthermore, 16% of these individuals did not have HIV testing within 14 days of initiating PrEP, and 13% were never evaluated for hepatitis B infection.⁸

Pharmacists are highly accessible health care professionals (HCPs): More than 90% of Americans live within 5 miles of a community pharmacy.⁹ Pharmacists play an integral role within the outpatient health care team and have been responsible for improvements in health care outcomes for a variety of chronic conditions and immunization practices.^10-13 Additionally, community pharmacists have provided vital access to care during the COVID-19 pandemic.¹⁴ The clinical pharmacist practitioner (CPP) is an innovative and advanced role within the Veterans Health Administration (VHA), functioning with a scope of practice and prescribing privileges to provide direct patient care.¹⁵

CPPs are well suited to address the need for increased access, capacity, and timely provision of PrEP, especially in areas where HIV acquisition rates are high or in areas with reduced access to care. We describe a model for a pharmacist-led HIV PrEP program (Pharm-PrEP) to increase access to PrEP. A similar program could be adapted to further expand the use of PrEP in other health care systems and community settings.

Pharm-PrEP Program Description

The Veterans Affairs Greater Los Angeles Healthcare System (VAGLAHCS) provides health care services at 11 locations in southern California and serves > 86,000 veterans. The VAGLAHCS pharmacy staff includes 33 CPPs who practice in more than 9 clinical service lines. HIV PrEP services are available through the infectious diseases (ID) service for veterans wishing to begin or continue PrEP or for those identified as high risk. HIV PrEP consultations are placed by the referring HCP to the ID service for scheduling and evaluation. Prior to implementation of the pharmacist-managed PrEP clinic, 2 ID physician assistants (PAs) were responsible for PrEP evaluation, initiation, and follow-up. Each PA had 1 half-day face-to-face clinic and 1 PA had an additional half-day telehealth clinic. About 100 PrEP patients were followed by the ID group.

In July 2019, through collaboration with the ID service, a pharmacy PrEP clinic was created to increase access for veterans to initiate or continue PrEP. This clinic included 1 ID-trained CPP and 1 postgraduate-year-2 pharmacy resident. The CPP initiates and monitors veterans for HIV PrEP with prescribing privileges under a defined scope of practice.

Awareness of this novel service was raised through in-service training sessions for primary care and women’s health clinics. Referrals are generated directly from primary care practitioners (PCPs) or emergency department (ED) visits and are accepted on a continuing basis. Visits with the CPP are conducted in person or through telehealth services based on patient preference. Direct CPP patient care appointments involve a standardized assessment and discussion of patient HIV transmission risk, a review of social and sexual history, sexual practices and HIV risk, clinical evidence of acute HIV or other sexually transmitted infection (STI) symptoms, follow-up PrEP monitoring requirements, and counseling on appropriate PrEP use. CPPs can order laboratory tests, bone densitometry (DEXA scan), immunizations, PrEP, and STI treatment as required. ID service physicians are available during CPP visits for further assessment or consultation. While initially most visits are conducted in person, follow-up visits by telehealth or video have become predominant; most patients prefer these modalities, citing convenience, flexibility, and the ability to obtain laboratory tests in advance. Use of telephone and video is intended to reduce patient loss to follow-up.

All required baseline laboratory panels for PrEP monitoring are ordered and interpreted by the CPP in accordance with CDC guidelines.¹⁶ These include screening for syphilis, gonorrhea, and chlamydia; fourth-generation antibody-antigen HIV tests; renal function; viral hepatitis; and pregnancy. After reviewing screening results, the CPP will prescribe tenofovir disproxil fumarate/emtricitabine (TDF/FTC) or tenofovir alafenamide/emtricitabine (TAF/FTC) based on individual patient clinical characteristics, US Food and Drug Administration–approved labeling, and VA Pharmacy Benefits Management Criteria for Use. Initial prescriptions are for a 30-day supply with subsequent prescriptions for 90 days (no refills), providing follow-up HIV testing is completed.

Follow-up PrEP visits are scheduled about every 3 months with some overlap to avoid gaps in medication due to late laboratory testing or delayed receipt of mailed medications. The only laboratory testing strictly required each quarter before PrEP renewal is HIV and pregnancy testing. Other screenings, including STIs and renal function are completed at least every 6 months or more frequently, if indicated, based on individual risk factors. Hepatitis C antibody testing is conducted annually if the patient has ongoing risk factors. Treatment of gonorrhea/chlamydia and syphilis for patients with positive test results is also initiated by the CPP, including recommending antimicrobial regimens. Additional interventions conducted as part of the clinic include indicated vaccinations (meningococcal, human papillomavirus, hepatitis A and B), and DEXA scans. Collaboration with ID service attendings and PAs is conducted on an as-needed basis via direct consultation in the colocated clinic or through email or messaging.

Periodic surveillance of a local dashboard of veterans eligible for HIV PrEP is conducted to re-engage veterans in care who may have been lost to follow-up, along with periodic review of a local STI dashboard. These dashboards capture population-based data to identify patients who may benefit from additional STI screenings as well as potential candidates for HIV PrEP. Clinicians can review their patient panel to target individuals who may be due for specific actions. Patients are identified as needing cotesting if they screen positive for ≥ 1 STIs but have not had a concurrent or subsequent full screening panel (gonorrhea, chlamydia, syphilis, and HIV). Cotesting for bacterial STIs and HIV at the time of an encounter has been promoted to expedite STI identification and treatment and limit community transmission. These reports also identify patients who may be potential candidates for HIV PrEP, based on a history of positive screenings, frequent STI testing, recent prescriptions for postexposure prophylaxis (PEP) or encounters with specific International Classification of Diseases codes associated with high-risk practices.

Clinic Quality of Care

From July 2019 to March 2020, 53 veterans were managed by the pharm-PrEP clinic in 98 encounters. Seventy percent of encounters were in-person (Table 1).

Baseline information collected included demographics, documented patient-reported risk factors, fourth-generation HIV screening test results, STI status, viral hepatitis serologies, and renal function test results. Information collected every 3 to 6 months included STI status, fourth-generation HIV screening test results, renal function test results, adherence to therapy, changes in risk factors, and prescription refill data. Additional interventions conducted as part of clinic workflow included DEXA scans, vaccinations, and active prescriptions for condoms.

Baseline Characteristics

Pharm-PrEP clinic patients were predominantly male (94%), and a majority indicated White race with a median age of 38 years (range, 24-80 years).

Veterans referred to the clinic had up to 5 risk factors for PrEP initiation. The most common risk factors were inconsistent condom use (62%), multiple sexual partners of unknown HIV status (62%), MSM (57%), STI history (38%), bisexual partners (25%), and HIV-positive sexual partners (11%). One of the 53 individuals referred for PrEP had no risk factors and did not initiate PrEP. Two individuals declined initiation of PrEP after consultation. Twenty six of 53 veterans at baseline continued their use of PrEP following transfer to clinic CPP management; 24 of 27 veterans not currently using PrEP (89%) started or restarted lapsed PrEP use following CPP consultation.

HIV and STI Screening

No individuals tested positive for HIV at baseline (n = 52) or while on PrEP. PrEP was not renewed for 3 patients that did follow through with HIV testing. The median number of days an HIV test was completed prior to initial PrEP and PrEP renewal was 4 days and < 7 days, respectively, both of which are below the recommended maximal interval of 7 days, according to CDC PrEP guidelines. Some postinitiation HIV testing occurred using a longer interval of 14 days, in accordance with VA National Criteria for Use of PrEP. This modification allowed more flexibility as a majority of PrEP prescriptions are sent to veterans via mail. The CPP reviewing HIV test results was able to expedite the processing and mailing of PrEP prescriptions if deemed appropriate, ie, the HIV test was negative. This approach was not used if a patient had high-risk exposures without PrEP during the time between collection of the HIV test and mailing of the prescription.

STI screening is a vital component of the Pharm-PrEP clinic and helped identify 4 patients with gonorrhea/chlamydia at baseline and 1 with syphilis after initiation of PrEP. All patients were prescribed antibiotics at the screening. Los Angeles County has high rates of STI transmission;thus implementation of clinic processes allowing the CPP to screen for STIs, interpret test results, and treat patients with STIs is vital to limit spread in the community.¹⁷

Selection of PrEP Regimen

The majority of individuals in the cohort received TDF/FTC for PrEP; TAF/FTC was restricted to individuals who had documented renal dysfunction or bone loss (Table 3).

Six DEXA scans were completed by the end of the evaluation period and 2 had abnormal results. One patient discontinued TDF/FTC and reinitiated with TAF/FTC. The other was switched to TAF/FTC 1 month after initiation.

Follow-Up Visits

The median number of visits per patient was 2. The median time between visits was in accordance with recommended follow-up intervals with 35 days between visits 1 and 2, 60 days between visits 2 and 3, and 88 days thereafter. In all, 10 veterans (20%) stopped PrEP: 4 (8%) were lost to follow-up; 3 (6%) had sustained behavior changes decreasing their HIV exposure risk; 2 (4%) were concerned about ADRs; and 1 (2%) moved out of state. Even after including those patients with a decrease in HIV exposure risk who no longer required PrEP, our 20% discontinuation rate was lower than those reported in other studies that showed a wide variation in PrEP discontinuation rates ranging from 33% to 62%.^18-20

Challenges

Some challenges with the implementation of the clinic included logistic and operational barriers, such as developing clinical pathways and managing workflow to facilitate vaccinations or STI treatment for individuals using video or telehealth services, as well as encouraging referrals from PCPs. These challenges were addressed by providing periodic targeted in-service training sessions to primary care teams to increase awareness of the Pharm-PrEP clinic. Collaboration with the ID service and ED allowed implementation of a direct pathway for patients initiated on nonoccupational HIV PEP after a high-risk exposure to be evaluated for transition to HIV PrEP. This PEP-2-PrEP pathway was designed to decrease barriers to follow-up for high-risk individuals who had recently received PEP in the ED. The CPP plays an active, integral role in managing patient care in the PEP-2-PrEP pathway.

Pharmacist-Led PrEP Care

The implementation of the VAGLAHCS Pharm-PrEP clinic demonstrates how CPPs can expand access and manage HIV PrEP with high reliability. Key factors for successfully integrating CPPs as PrEP prescribers include identifying physician champions; using in-services or other training platforms to raise awareness among potential referring HCPs and stimulate referrals; and developing processes to identify high-risk veterans. Also, nontraditional modes of care, such as video or telehealth appointments, can increase access and expand the volume of patient care visits. Such modalities are useful for PrEP management when combined with a well-defined operational process for laboratory specimen collection before appointments. This system is particularly well suited to increasing access to PrEP for patients who live in rural or highly rural areas that are medically underserved or who have difficulty traveling to a clinical facility for an in-person visit.

Although community health care organizations and HCPs face pay barriers not present in the VHA system, several studies have demonstrated feasability of pharmacist-led clinics in private health care systems.^21-24 Havens and colleagues described a PrEP program affilitated with an university that assessed patient satisfaction and pharmacist acceptability with this new service.²² The results of surveys reported high patient satisfaction and pharmacist acceptability.²³ Tung and colleagues described a PrEP clinic located in a community pharmacy with the ability to bill for pharmacist and laboratory services in addition to medication costs.²⁴ These studies, along with our findings, demonstrate that CPPs are well positioned to manage HIV PrEP in the community. Leveraging the skills and experience of CPPs to address poor uptake and access to PrEP should be a central component in achieving the goals of the Ending the HIV Epidemic initiative, given that pharmacists are one of the most accessible groups of HCPs nationally.

Pharmacist prescriptive authority varies across different states and may depend on collaborative practice agreements, statewide protocols, or class-specific prescribing.²⁵ For example, California was among the first states to authorize initiation and prescription of HIV PrEP and PEP by pharmacists in specified amounts after appropriate training.²⁶ Nationwide support for similar policies in the community and within health care systems will be critical to the successful implementation and functioning of pharmacy-led PrEP clinics.

Conclusions

The success of this Pharm-PrEP clinic was largely due to a collaborative, interdisciplinary effort to implement this new clinic process and incorporate the CPP into the general ID outpatient clinic, while allowing flexibility in scheduling and use of different encounter modalities for patients. Deploying pharmacists as PrEP prescribers can help health care systems increase PrEP access and capacity and improve efforts to achieve the goals of the Ending the HIV Epidemic. This type of program can be a model for other health care organizations and systems to implement pharmacy-led PrEP clinics and expand telehealth modalities to deliver PrEP.

Acknowledgments

The infectious diseases service at the Veterans Affairs Greater Los Angeles Healthcare System and the veterans we serve.

The US Department of Health and Human Services (HHS) Ending the HIV Epidemic framework aims to decrease HIV infections in the United States by 90% before 2030.¹ Achieving this goal requires identifying persons at high risk for HIV and ensuring timely and efficient access to HIV preexposure prophylaxis (PrEP).^2-5 However, despite its commercial availability since 2012, community uptake of PrEP is low.⁶ In 2019, < 25% of Americans who could benefit from PrEP were using this preventive therapy.⁷ Poor uptake of PrEP has also been documented among veterans and US military service members. National data on men in the military and men who have sex with men (MSM) in the military suggest that about 12,000 service members are eligible for PrEP; however, only 2000 service members and their beneficiaries accessed PrEP in February 2017.⁸

A review of health records of US military service members conducted from 2014 to 2016 indicated that most patients who received PrEP did not receive recommended monitoring in accordance with the Centers for Disease Control and Prevention (CDC) guidelines. Furthermore, 16% of these individuals did not have HIV testing within 14 days of initiating PrEP, and 13% were never evaluated for hepatitis B infection.⁸

Pharmacists are highly accessible health care professionals (HCPs): More than 90% of Americans live within 5 miles of a community pharmacy.⁹ Pharmacists play an integral role within the outpatient health care team and have been responsible for improvements in health care outcomes for a variety of chronic conditions and immunization practices.^10-13 Additionally, community pharmacists have provided vital access to care during the COVID-19 pandemic.¹⁴ The clinical pharmacist practitioner (CPP) is an innovative and advanced role within the Veterans Health Administration (VHA), functioning with a scope of practice and prescribing privileges to provide direct patient care.¹⁵

CPPs are well suited to address the need for increased access, capacity, and timely provision of PrEP, especially in areas where HIV acquisition rates are high or in areas with reduced access to care. We describe a model for a pharmacist-led HIV PrEP program (Pharm-PrEP) to increase access to PrEP. A similar program could be adapted to further expand the use of PrEP in other health care systems and community settings.

Pharm-PrEP Program Description

The Veterans Affairs Greater Los Angeles Healthcare System (VAGLAHCS) provides health care services at 11 locations in southern California and serves > 86,000 veterans. The VAGLAHCS pharmacy staff includes 33 CPPs who practice in more than 9 clinical service lines. HIV PrEP services are available through the infectious diseases (ID) service for veterans wishing to begin or continue PrEP or for those identified as high risk. HIV PrEP consultations are placed by the referring HCP to the ID service for scheduling and evaluation. Prior to implementation of the pharmacist-managed PrEP clinic, 2 ID physician assistants (PAs) were responsible for PrEP evaluation, initiation, and follow-up. Each PA had 1 half-day face-to-face clinic and 1 PA had an additional half-day telehealth clinic. About 100 PrEP patients were followed by the ID group.

In July 2019, through collaboration with the ID service, a pharmacy PrEP clinic was created to increase access for veterans to initiate or continue PrEP. This clinic included 1 ID-trained CPP and 1 postgraduate-year-2 pharmacy resident. The CPP initiates and monitors veterans for HIV PrEP with prescribing privileges under a defined scope of practice.

Awareness of this novel service was raised through in-service training sessions for primary care and women’s health clinics. Referrals are generated directly from primary care practitioners (PCPs) or emergency department (ED) visits and are accepted on a continuing basis. Visits with the CPP are conducted in person or through telehealth services based on patient preference. Direct CPP patient care appointments involve a standardized assessment and discussion of patient HIV transmission risk, a review of social and sexual history, sexual practices and HIV risk, clinical evidence of acute HIV or other sexually transmitted infection (STI) symptoms, follow-up PrEP monitoring requirements, and counseling on appropriate PrEP use. CPPs can order laboratory tests, bone densitometry (DEXA scan), immunizations, PrEP, and STI treatment as required. ID service physicians are available during CPP visits for further assessment or consultation. While initially most visits are conducted in person, follow-up visits by telehealth or video have become predominant; most patients prefer these modalities, citing convenience, flexibility, and the ability to obtain laboratory tests in advance. Use of telephone and video is intended to reduce patient loss to follow-up.

All required baseline laboratory panels for PrEP monitoring are ordered and interpreted by the CPP in accordance with CDC guidelines.¹⁶ These include screening for syphilis, gonorrhea, and chlamydia; fourth-generation antibody-antigen HIV tests; renal function; viral hepatitis; and pregnancy. After reviewing screening results, the CPP will prescribe tenofovir disproxil fumarate/emtricitabine (TDF/FTC) or tenofovir alafenamide/emtricitabine (TAF/FTC) based on individual patient clinical characteristics, US Food and Drug Administration–approved labeling, and VA Pharmacy Benefits Management Criteria for Use. Initial prescriptions are for a 30-day supply with subsequent prescriptions for 90 days (no refills), providing follow-up HIV testing is completed.

Follow-up PrEP visits are scheduled about every 3 months with some overlap to avoid gaps in medication due to late laboratory testing or delayed receipt of mailed medications. The only laboratory testing strictly required each quarter before PrEP renewal is HIV and pregnancy testing. Other screenings, including STIs and renal function are completed at least every 6 months or more frequently, if indicated, based on individual risk factors. Hepatitis C antibody testing is conducted annually if the patient has ongoing risk factors. Treatment of gonorrhea/chlamydia and syphilis for patients with positive test results is also initiated by the CPP, including recommending antimicrobial regimens. Additional interventions conducted as part of the clinic include indicated vaccinations (meningococcal, human papillomavirus, hepatitis A and B), and DEXA scans. Collaboration with ID service attendings and PAs is conducted on an as-needed basis via direct consultation in the colocated clinic or through email or messaging.

Periodic surveillance of a local dashboard of veterans eligible for HIV PrEP is conducted to re-engage veterans in care who may have been lost to follow-up, along with periodic review of a local STI dashboard. These dashboards capture population-based data to identify patients who may benefit from additional STI screenings as well as potential candidates for HIV PrEP. Clinicians can review their patient panel to target individuals who may be due for specific actions. Patients are identified as needing cotesting if they screen positive for ≥ 1 STIs but have not had a concurrent or subsequent full screening panel (gonorrhea, chlamydia, syphilis, and HIV). Cotesting for bacterial STIs and HIV at the time of an encounter has been promoted to expedite STI identification and treatment and limit community transmission. These reports also identify patients who may be potential candidates for HIV PrEP, based on a history of positive screenings, frequent STI testing, recent prescriptions for postexposure prophylaxis (PEP) or encounters with specific International Classification of Diseases codes associated with high-risk practices.

Clinic Quality of Care

From July 2019 to March 2020, 53 veterans were managed by the pharm-PrEP clinic in 98 encounters. Seventy percent of encounters were in-person (Table 1).

Baseline information collected included demographics, documented patient-reported risk factors, fourth-generation HIV screening test results, STI status, viral hepatitis serologies, and renal function test results. Information collected every 3 to 6 months included STI status, fourth-generation HIV screening test results, renal function test results, adherence to therapy, changes in risk factors, and prescription refill data. Additional interventions conducted as part of clinic workflow included DEXA scans, vaccinations, and active prescriptions for condoms.

Baseline Characteristics

Pharm-PrEP clinic patients were predominantly male (94%), and a majority indicated White race with a median age of 38 years (range, 24-80 years).

Veterans referred to the clinic had up to 5 risk factors for PrEP initiation. The most common risk factors were inconsistent condom use (62%), multiple sexual partners of unknown HIV status (62%), MSM (57%), STI history (38%), bisexual partners (25%), and HIV-positive sexual partners (11%). One of the 53 individuals referred for PrEP had no risk factors and did not initiate PrEP. Two individuals declined initiation of PrEP after consultation. Twenty six of 53 veterans at baseline continued their use of PrEP following transfer to clinic CPP management; 24 of 27 veterans not currently using PrEP (89%) started or restarted lapsed PrEP use following CPP consultation.

HIV and STI Screening

No individuals tested positive for HIV at baseline (n = 52) or while on PrEP. PrEP was not renewed for 3 patients that did follow through with HIV testing. The median number of days an HIV test was completed prior to initial PrEP and PrEP renewal was 4 days and < 7 days, respectively, both of which are below the recommended maximal interval of 7 days, according to CDC PrEP guidelines. Some postinitiation HIV testing occurred using a longer interval of 14 days, in accordance with VA National Criteria for Use of PrEP. This modification allowed more flexibility as a majority of PrEP prescriptions are sent to veterans via mail. The CPP reviewing HIV test results was able to expedite the processing and mailing of PrEP prescriptions if deemed appropriate, ie, the HIV test was negative. This approach was not used if a patient had high-risk exposures without PrEP during the time between collection of the HIV test and mailing of the prescription.

STI screening is a vital component of the Pharm-PrEP clinic and helped identify 4 patients with gonorrhea/chlamydia at baseline and 1 with syphilis after initiation of PrEP. All patients were prescribed antibiotics at the screening. Los Angeles County has high rates of STI transmission;thus implementation of clinic processes allowing the CPP to screen for STIs, interpret test results, and treat patients with STIs is vital to limit spread in the community.¹⁷

Selection of PrEP Regimen

The majority of individuals in the cohort received TDF/FTC for PrEP; TAF/FTC was restricted to individuals who had documented renal dysfunction or bone loss (Table 3).

Six DEXA scans were completed by the end of the evaluation period and 2 had abnormal results. One patient discontinued TDF/FTC and reinitiated with TAF/FTC. The other was switched to TAF/FTC 1 month after initiation.

Follow-Up Visits

The median number of visits per patient was 2. The median time between visits was in accordance with recommended follow-up intervals with 35 days between visits 1 and 2, 60 days between visits 2 and 3, and 88 days thereafter. In all, 10 veterans (20%) stopped PrEP: 4 (8%) were lost to follow-up; 3 (6%) had sustained behavior changes decreasing their HIV exposure risk; 2 (4%) were concerned about ADRs; and 1 (2%) moved out of state. Even after including those patients with a decrease in HIV exposure risk who no longer required PrEP, our 20% discontinuation rate was lower than those reported in other studies that showed a wide variation in PrEP discontinuation rates ranging from 33% to 62%.^18-20

Challenges

Some challenges with the implementation of the clinic included logistic and operational barriers, such as developing clinical pathways and managing workflow to facilitate vaccinations or STI treatment for individuals using video or telehealth services, as well as encouraging referrals from PCPs. These challenges were addressed by providing periodic targeted in-service training sessions to primary care teams to increase awareness of the Pharm-PrEP clinic. Collaboration with the ID service and ED allowed implementation of a direct pathway for patients initiated on nonoccupational HIV PEP after a high-risk exposure to be evaluated for transition to HIV PrEP. This PEP-2-PrEP pathway was designed to decrease barriers to follow-up for high-risk individuals who had recently received PEP in the ED. The CPP plays an active, integral role in managing patient care in the PEP-2-PrEP pathway.

Pharmacist-Led PrEP Care

The implementation of the VAGLAHCS Pharm-PrEP clinic demonstrates how CPPs can expand access and manage HIV PrEP with high reliability. Key factors for successfully integrating CPPs as PrEP prescribers include identifying physician champions; using in-services or other training platforms to raise awareness among potential referring HCPs and stimulate referrals; and developing processes to identify high-risk veterans. Also, nontraditional modes of care, such as video or telehealth appointments, can increase access and expand the volume of patient care visits. Such modalities are useful for PrEP management when combined with a well-defined operational process for laboratory specimen collection before appointments. This system is particularly well suited to increasing access to PrEP for patients who live in rural or highly rural areas that are medically underserved or who have difficulty traveling to a clinical facility for an in-person visit.

Although community health care organizations and HCPs face pay barriers not present in the VHA system, several studies have demonstrated feasability of pharmacist-led clinics in private health care systems.^21-24 Havens and colleagues described a PrEP program affilitated with an university that assessed patient satisfaction and pharmacist acceptability with this new service.²² The results of surveys reported high patient satisfaction and pharmacist acceptability.²³ Tung and colleagues described a PrEP clinic located in a community pharmacy with the ability to bill for pharmacist and laboratory services in addition to medication costs.²⁴ These studies, along with our findings, demonstrate that CPPs are well positioned to manage HIV PrEP in the community. Leveraging the skills and experience of CPPs to address poor uptake and access to PrEP should be a central component in achieving the goals of the Ending the HIV Epidemic initiative, given that pharmacists are one of the most accessible groups of HCPs nationally.

Pharmacist prescriptive authority varies across different states and may depend on collaborative practice agreements, statewide protocols, or class-specific prescribing.²⁵ For example, California was among the first states to authorize initiation and prescription of HIV PrEP and PEP by pharmacists in specified amounts after appropriate training.²⁶ Nationwide support for similar policies in the community and within health care systems will be critical to the successful implementation and functioning of pharmacy-led PrEP clinics.

Conclusions

The success of this Pharm-PrEP clinic was largely due to a collaborative, interdisciplinary effort to implement this new clinic process and incorporate the CPP into the general ID outpatient clinic, while allowing flexibility in scheduling and use of different encounter modalities for patients. Deploying pharmacists as PrEP prescribers can help health care systems increase PrEP access and capacity and improve efforts to achieve the goals of the Ending the HIV Epidemic. This type of program can be a model for other health care organizations and systems to implement pharmacy-led PrEP clinics and expand telehealth modalities to deliver PrEP.

Acknowledgments

The infectious diseases service at the Veterans Affairs Greater Los Angeles Healthcare System and the veterans we serve.

The Food and Drug Administration has cleared Beta Bionics’s iLet ACE Pump and the iLet Dosing Decision Software for people ages 6 years and older with type 1 diabetes.
 

Working together with a previously cleared integrated continuous glucose monitor (CGM), the entire new system is called the iLet Bionic Pancreas. It differs from current automated insulin delivery (AID) systems in its increased level of automation. The adaptive algorithm is initialized using only the patient’s body weight, without other insulin dosing parameters. Rather than entering specific carbohydrate counts, users only input whether the carbohydrate amount in the meal is “small,” “medium,” or “large.” The algorithm adapts over time to users’ individual 24/7 insulin needs.

Pivotal data for the system were presented in June 2022 at the annual scientific sessions of the American Diabetes Association.

In the 16-center trial involving 440 adults and children 6 years and older with type 1 diabetes, the system reduced hemoglobin A1c by 0.5 percentage points by 13 weeks, without increased hypoglycemia. They spent an average of 2.6 hours more time in range, compared with standard of care (either currently available AIDs, stand-alone pump and CGM devices, or multiple daily injections plus CGM).

The FDA had granted the iLet a breakthrough device designation in December 2019.

Anne L. Peters, MD, a professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes program, commented on the pivotal study and the system in June 2022. She called the study “cool” because it enrolled more than 25% minority individuals “who aren’t routinely studied in these insulin device trials” and also that it included people with a range of baseline A1c levels, with more than 30% greater than 8%.

Regarding the system’s algorithm, she pointed out that it “doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.”

That might represent a limitation for some with type 1 diabetes, study coprincipal investigator Roy W. Beck, MD, PhD, said in an interview during the ADA meeting. “The iLet could dramatically reduce type 1 diabetes management burden for many patients, but it might not suit everyone. For example, somebody who’s very compulsive and has an A1c of 6.5% and is used to manipulating what they do, this is probably not a good system for them because the system is kind of taking over.”

On the other hand, Dr. Peters said, “I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.”

The “bionic pancreas” was originally conceived as a dual-hormone system including glucagon delivery as well as insulin. Beta Bionics is continuing to work with the FDA on that front.

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

The Food and Drug Administration has cleared Beta Bionics’s iLet ACE Pump and the iLet Dosing Decision Software for people ages 6 years and older with type 1 diabetes.
 

Working together with a previously cleared integrated continuous glucose monitor (CGM), the entire new system is called the iLet Bionic Pancreas. It differs from current automated insulin delivery (AID) systems in its increased level of automation. The adaptive algorithm is initialized using only the patient’s body weight, without other insulin dosing parameters. Rather than entering specific carbohydrate counts, users only input whether the carbohydrate amount in the meal is “small,” “medium,” or “large.” The algorithm adapts over time to users’ individual 24/7 insulin needs.

Pivotal data for the system were presented in June 2022 at the annual scientific sessions of the American Diabetes Association.

In the 16-center trial involving 440 adults and children 6 years and older with type 1 diabetes, the system reduced hemoglobin A1c by 0.5 percentage points by 13 weeks, without increased hypoglycemia. They spent an average of 2.6 hours more time in range, compared with standard of care (either currently available AIDs, stand-alone pump and CGM devices, or multiple daily injections plus CGM).

The FDA had granted the iLet a breakthrough device designation in December 2019.

Anne L. Peters, MD, a professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes program, commented on the pivotal study and the system in June 2022. She called the study “cool” because it enrolled more than 25% minority individuals “who aren’t routinely studied in these insulin device trials” and also that it included people with a range of baseline A1c levels, with more than 30% greater than 8%.

Regarding the system’s algorithm, she pointed out that it “doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.”

That might represent a limitation for some with type 1 diabetes, study coprincipal investigator Roy W. Beck, MD, PhD, said in an interview during the ADA meeting. “The iLet could dramatically reduce type 1 diabetes management burden for many patients, but it might not suit everyone. For example, somebody who’s very compulsive and has an A1c of 6.5% and is used to manipulating what they do, this is probably not a good system for them because the system is kind of taking over.”

On the other hand, Dr. Peters said, “I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.”

The “bionic pancreas” was originally conceived as a dual-hormone system including glucagon delivery as well as insulin. Beta Bionics is continuing to work with the FDA on that front.

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

The Food and Drug Administration has cleared Beta Bionics’s iLet ACE Pump and the iLet Dosing Decision Software for people ages 6 years and older with type 1 diabetes.
 

Working together with a previously cleared integrated continuous glucose monitor (CGM), the entire new system is called the iLet Bionic Pancreas. It differs from current automated insulin delivery (AID) systems in its increased level of automation. The adaptive algorithm is initialized using only the patient’s body weight, without other insulin dosing parameters. Rather than entering specific carbohydrate counts, users only input whether the carbohydrate amount in the meal is “small,” “medium,” or “large.” The algorithm adapts over time to users’ individual 24/7 insulin needs.

Pivotal data for the system were presented in June 2022 at the annual scientific sessions of the American Diabetes Association.

In the 16-center trial involving 440 adults and children 6 years and older with type 1 diabetes, the system reduced hemoglobin A1c by 0.5 percentage points by 13 weeks, without increased hypoglycemia. They spent an average of 2.6 hours more time in range, compared with standard of care (either currently available AIDs, stand-alone pump and CGM devices, or multiple daily injections plus CGM).

The FDA had granted the iLet a breakthrough device designation in December 2019.

Anne L. Peters, MD, a professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes program, commented on the pivotal study and the system in June 2022. She called the study “cool” because it enrolled more than 25% minority individuals “who aren’t routinely studied in these insulin device trials” and also that it included people with a range of baseline A1c levels, with more than 30% greater than 8%.

Regarding the system’s algorithm, she pointed out that it “doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.”

That might represent a limitation for some with type 1 diabetes, study coprincipal investigator Roy W. Beck, MD, PhD, said in an interview during the ADA meeting. “The iLet could dramatically reduce type 1 diabetes management burden for many patients, but it might not suit everyone. For example, somebody who’s very compulsive and has an A1c of 6.5% and is used to manipulating what they do, this is probably not a good system for them because the system is kind of taking over.”

On the other hand, Dr. Peters said, “I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.”

The “bionic pancreas” was originally conceived as a dual-hormone system including glucagon delivery as well as insulin. Beta Bionics is continuing to work with the FDA on that front.

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

Mantle cell lymphoma (MCL) is a rare, B-cell non-Hodgkin lymphoma whose biological heterogeneity has long challenged researchers and clinicians. There are no firmly-established therapies, and many individuals experience relapse even after successful treatment. There is a clear unmet need in MCL in the relapsed setting. In recent years, researchers have worked to address this need, demonstrating efficacy with covalent Bruton tyrosine kinase (BTK) inhibitors, led by ibrutinib, and anti-CD19 chimeric antigen receptor T-cell therapy. While these are helpful additions, relapse remains a challenge. 

Fortunately, progress continues. Owing to encouraging results in recent trials, individuals with relapsed/refractory MCL are now experiencing clinical benefit from the noncovalent BTK inhibitor pirtrobrutinib. Investigational bispecific antibody (bsAb) therapy awaits in the wings. 

Similarly, both younger and older patients with treatment naïve MCL could soon see improvement from the addition of BTK inhibitors to each age group’s standard treatment option. The following is a description of recent developments and their potential implications for practice.  

One of the most exciting developments is the US Food and Drug Administration’s accelerated approval of pirtrobrutinib. A noncovalent BTK inhibitor, pirtrobrutinib has been found to have activity in individuals with MCL who have failed on multiple therapies, including standard BTK inhibitors. Pirtrobrutinib targets certain mutations in the BTK protein that are associated with resistance to covalent BTK inhibitors. In addition to resistance, some patients discontinue treatment with non-reversible BTK inhibitors because of intolerable toxicity. 

Approval of pirtrobrutinib was based on an evaluation involving 120 individuals (median age 71) who were previously treated with a non-reversible BTK inhibitor. Two-thirds were previously treated with ibrutinib; 30% with acalabrutinib, and 8% zanubrutinib (some received more than one BTK inhibitor previously). The vast majority (83%) discontinued treatment due to refractory or progressive disease; 10% stopped due to toxicity; and the remainder halted treatment for other reasons. 

Six in every 10 of the participants were classified on the MCL International Prognostic Index as intermediate; one-fourth were classified as high; and the remainder low. Patients received 200 mg of pirtrobrutinib once a day until disease either progressed or they experienced intolerable toxicity. Among the results:

• Overall response rate was 50%; 13% responded completely

• Median duration of response was 8.3 months

• Duration of response rate at 6 months was 65%

• Grade 3 or 4 abnormalities experienced by 10% or more of participants included decreased neutrophil counts, lymphocyte counts, and platelet counts

Further, bsAb therapy targeting CD20-CD3 is not yet approved but is showing promise as a potential therapy following BTK inhibitor failure. The treatment consists of an antibody containing two prongs. One is a CD20 protein that attaches to the lymphoma cell. The other is an anti-CD3 antibody that attaches to the T cell to bring the patient’s own T cells closer to the lymphoma to increase the cell kill. 

Preliminary studies evaluating bsAbs in individuals with MCL, many of whom have failed on multiple other types of therapies, show a remarkably high response rate. In one such investigation, the bsAb glofitamab was given to 21 individuals as monotherapy following pretreatment with obinutuzumab. The regimen produced an overall response rate of 81% (n = 17) and a complete response rate of 68% (n = 14). Response was similar in participants who had and had not received prior BTK therapy. Among those who achieved a complete response, median duration was 2.4 months, and 12 of those who reached a complete response were still in remission at the study’s data cutoff point. 

For younger individuals with treatment-naïve MCL, the current standard is chemotherapy and autologous stem-cell transplant (ASCT). For older individuals the standard is chemoimmunotherapy. The replacement or addition of the BTK inhibitor ibrutinib to these regimens is showing the promise of added clinical benefit in both age contingents. 

Investigators presented results of the three-arm TRIANGLE trial at the 64th ASH Annual Meeting in December 2022. The study compared 1) chemotherapy followed by ASCT; 2) ibrutinib plus chemotherapy followed by ASCT and ibrutinib maintenance; and 3) ibrutinib plus chemotherapy followed by ibrutinib maintenance. Participants (n = 870) ≤ 65 years of age (median age 57) with previously untreated advanced-stage MCL were randomized to 1 of the 3 regimens. Investigators looked at overall response, complete response, and failure-free survival rates (FFS). Among the results: 

• Overall response rates were 98% in the 2 groups whose treatments included ibrutinib, versus 94% in the chemotherapy followed by ASCT group. 

• Complete response rates were 45% and 36%, respectively.

• The non-ibrutinib regimen did not attain FFS superiority over ibrutinib plus chemotherapy, with a 3-year FFS rate of 72% and 86%, respectively (p=0.9979, hazard ratio [HR]: 1.77).

• Ibrutinib plus chemotherapy was shown to be superior to chemotherapy/ASCT, with a 3-year FFS rate of 88% and 72%, respectively (p=0.0008, HR: 0.52).

• The only adverse event differences of note occurred during maintenance treatment; there were significantly more grade 3-5 adverse events in the ibrutinib/chemotherapy/ASCT group, compared with the other 2 contingents.

Researchers noted in materials accompanying their presentation that, “It has been clearly demonstrated that the current standard high-dose regimen is not superior to the new ibrutinib-containing regimen without ASCT. More follow-up is needed to clarify the role of ASCT in the context of ibrutinib-containing treatment. However, the current results already support the use of ibrutinib in the first-line treatment of younger MCL patients.”

It also appears that ibrutinib added to standard chemoimmunotherapy can improve outcomes in older individuals with treatment-naïve MCL. In 2022, researchers published results from the international, randomized, double-blind, phase 3 SHINE trial. Participants (n = 523) were ≥ 65 years of age with previously untreated MCL and were randomized to receive either ibrutinib 560 mg daily or placebo added to chemoimmunotherapy consisting of bendamustine and rituximab every 4 weeks for 6 cycles. Individuals with a partial or complete response continued treatment every 8 weeks for up to 12 more doses. Investigators looked primarily at progression-free survival (PFS), as well as complete response, undetectable minimal residual disease, and time to worsening. Among the results: 

• 116 participants (44%) in the ibrutinib group experienced disease progression or died, compared with 152 (58%) in the placebo contingent. 

• Median PFS was 80.6 months and 52.9 months, respectively.

• PFS benefit was seen across most subgroups (patients categorized as high risk, and those with TP53 mutations did not benefit).

• Complete response was seen in 66% and 58% of participants, respectively.

• Undetectable minimal residual disease was observed in 62% and 57%, respectively.

• Deaths attributed to disease progression or adverse events occurred in 22% and 28%, respectively.

• Grade 3 or 4 adverse event incident rates were 82% and 77%, respectively.

Researchers noted that, “Given the shorter progression-free survival with current standard-care chemoimmunotherapy options, a prolongation of progression-free survival in response to primary therapy may provide patients with an improved opportunity for durable disease control in order to prevent or delay relapse.”

Data on the use of other BTK inhibitors as first-line treatment for MCL are forthcoming, including: 

• ECHO, a phase 3 trial assessing the efficacy of acalabrutinib versus placebo added to bendamustine and rituximab.

• MANGROVE, a phase 3 study comparing zanubrutinib plus rituximab versus bendamustine plus rituximab.

• ENRICH, a phase 2 study evaluating a chemotherapy-free option–ibrutinib and rituximab in older individuals.

• OASIS, a randomized, phase 2 trial comparing ibrutinib/anti-CD20 antibodies (Ab) and Ibrutinib/anti-CD20 Ab/venetoclax given as fixed duration combinations. 

The evolution of BTK inhibitors for relapsed MCL has great potential; further benefits continue to be explored.

Mantle cell lymphoma (MCL) is a rare, B-cell non-Hodgkin lymphoma whose biological heterogeneity has long challenged researchers and clinicians. There are no firmly-established therapies, and many individuals experience relapse even after successful treatment. There is a clear unmet need in MCL in the relapsed setting. In recent years, researchers have worked to address this need, demonstrating efficacy with covalent Bruton tyrosine kinase (BTK) inhibitors, led by ibrutinib, and anti-CD19 chimeric antigen receptor T-cell therapy. While these are helpful additions, relapse remains a challenge. 

Fortunately, progress continues. Owing to encouraging results in recent trials, individuals with relapsed/refractory MCL are now experiencing clinical benefit from the noncovalent BTK inhibitor pirtrobrutinib. Investigational bispecific antibody (bsAb) therapy awaits in the wings. 

Similarly, both younger and older patients with treatment naïve MCL could soon see improvement from the addition of BTK inhibitors to each age group’s standard treatment option. The following is a description of recent developments and their potential implications for practice.  

One of the most exciting developments is the US Food and Drug Administration’s accelerated approval of pirtrobrutinib. A noncovalent BTK inhibitor, pirtrobrutinib has been found to have activity in individuals with MCL who have failed on multiple therapies, including standard BTK inhibitors. Pirtrobrutinib targets certain mutations in the BTK protein that are associated with resistance to covalent BTK inhibitors. In addition to resistance, some patients discontinue treatment with non-reversible BTK inhibitors because of intolerable toxicity. 

Approval of pirtrobrutinib was based on an evaluation involving 120 individuals (median age 71) who were previously treated with a non-reversible BTK inhibitor. Two-thirds were previously treated with ibrutinib; 30% with acalabrutinib, and 8% zanubrutinib (some received more than one BTK inhibitor previously). The vast majority (83%) discontinued treatment due to refractory or progressive disease; 10% stopped due to toxicity; and the remainder halted treatment for other reasons. 

Six in every 10 of the participants were classified on the MCL International Prognostic Index as intermediate; one-fourth were classified as high; and the remainder low. Patients received 200 mg of pirtrobrutinib once a day until disease either progressed or they experienced intolerable toxicity. Among the results:

• Overall response rate was 50%; 13% responded completely

• Median duration of response was 8.3 months

• Duration of response rate at 6 months was 65%

• Grade 3 or 4 abnormalities experienced by 10% or more of participants included decreased neutrophil counts, lymphocyte counts, and platelet counts

Further, bsAb therapy targeting CD20-CD3 is not yet approved but is showing promise as a potential therapy following BTK inhibitor failure. The treatment consists of an antibody containing two prongs. One is a CD20 protein that attaches to the lymphoma cell. The other is an anti-CD3 antibody that attaches to the T cell to bring the patient’s own T cells closer to the lymphoma to increase the cell kill. 

Preliminary studies evaluating bsAbs in individuals with MCL, many of whom have failed on multiple other types of therapies, show a remarkably high response rate. In one such investigation, the bsAb glofitamab was given to 21 individuals as monotherapy following pretreatment with obinutuzumab. The regimen produced an overall response rate of 81% (n = 17) and a complete response rate of 68% (n = 14). Response was similar in participants who had and had not received prior BTK therapy. Among those who achieved a complete response, median duration was 2.4 months, and 12 of those who reached a complete response were still in remission at the study’s data cutoff point. 

For younger individuals with treatment-naïve MCL, the current standard is chemotherapy and autologous stem-cell transplant (ASCT). For older individuals the standard is chemoimmunotherapy. The replacement or addition of the BTK inhibitor ibrutinib to these regimens is showing the promise of added clinical benefit in both age contingents. 

Investigators presented results of the three-arm TRIANGLE trial at the 64th ASH Annual Meeting in December 2022. The study compared 1) chemotherapy followed by ASCT; 2) ibrutinib plus chemotherapy followed by ASCT and ibrutinib maintenance; and 3) ibrutinib plus chemotherapy followed by ibrutinib maintenance. Participants (n = 870) ≤ 65 years of age (median age 57) with previously untreated advanced-stage MCL were randomized to 1 of the 3 regimens. Investigators looked at overall response, complete response, and failure-free survival rates (FFS). Among the results: 

• Overall response rates were 98% in the 2 groups whose treatments included ibrutinib, versus 94% in the chemotherapy followed by ASCT group. 

• Complete response rates were 45% and 36%, respectively.

• The non-ibrutinib regimen did not attain FFS superiority over ibrutinib plus chemotherapy, with a 3-year FFS rate of 72% and 86%, respectively (p=0.9979, hazard ratio [HR]: 1.77).

• Ibrutinib plus chemotherapy was shown to be superior to chemotherapy/ASCT, with a 3-year FFS rate of 88% and 72%, respectively (p=0.0008, HR: 0.52).

• The only adverse event differences of note occurred during maintenance treatment; there were significantly more grade 3-5 adverse events in the ibrutinib/chemotherapy/ASCT group, compared with the other 2 contingents.

Researchers noted in materials accompanying their presentation that, “It has been clearly demonstrated that the current standard high-dose regimen is not superior to the new ibrutinib-containing regimen without ASCT. More follow-up is needed to clarify the role of ASCT in the context of ibrutinib-containing treatment. However, the current results already support the use of ibrutinib in the first-line treatment of younger MCL patients.”

It also appears that ibrutinib added to standard chemoimmunotherapy can improve outcomes in older individuals with treatment-naïve MCL. In 2022, researchers published results from the international, randomized, double-blind, phase 3 SHINE trial. Participants (n = 523) were ≥ 65 years of age with previously untreated MCL and were randomized to receive either ibrutinib 560 mg daily or placebo added to chemoimmunotherapy consisting of bendamustine and rituximab every 4 weeks for 6 cycles. Individuals with a partial or complete response continued treatment every 8 weeks for up to 12 more doses. Investigators looked primarily at progression-free survival (PFS), as well as complete response, undetectable minimal residual disease, and time to worsening. Among the results: 

• 116 participants (44%) in the ibrutinib group experienced disease progression or died, compared with 152 (58%) in the placebo contingent. 

• Median PFS was 80.6 months and 52.9 months, respectively.

• PFS benefit was seen across most subgroups (patients categorized as high risk, and those with TP53 mutations did not benefit).

• Complete response was seen in 66% and 58% of participants, respectively.

• Undetectable minimal residual disease was observed in 62% and 57%, respectively.

• Deaths attributed to disease progression or adverse events occurred in 22% and 28%, respectively.

• Grade 3 or 4 adverse event incident rates were 82% and 77%, respectively.

Researchers noted that, “Given the shorter progression-free survival with current standard-care chemoimmunotherapy options, a prolongation of progression-free survival in response to primary therapy may provide patients with an improved opportunity for durable disease control in order to prevent or delay relapse.”

Data on the use of other BTK inhibitors as first-line treatment for MCL are forthcoming, including: 

• ECHO, a phase 3 trial assessing the efficacy of acalabrutinib versus placebo added to bendamustine and rituximab.

• MANGROVE, a phase 3 study comparing zanubrutinib plus rituximab versus bendamustine plus rituximab.

• ENRICH, a phase 2 study evaluating a chemotherapy-free option–ibrutinib and rituximab in older individuals.

• OASIS, a randomized, phase 2 trial comparing ibrutinib/anti-CD20 antibodies (Ab) and Ibrutinib/anti-CD20 Ab/venetoclax given as fixed duration combinations. 

The evolution of BTK inhibitors for relapsed MCL has great potential; further benefits continue to be explored.

Mantle cell lymphoma (MCL) is a rare, B-cell non-Hodgkin lymphoma whose biological heterogeneity has long challenged researchers and clinicians. There are no firmly-established therapies, and many individuals experience relapse even after successful treatment. There is a clear unmet need in MCL in the relapsed setting. In recent years, researchers have worked to address this need, demonstrating efficacy with covalent Bruton tyrosine kinase (BTK) inhibitors, led by ibrutinib, and anti-CD19 chimeric antigen receptor T-cell therapy. While these are helpful additions, relapse remains a challenge. 

Fortunately, progress continues. Owing to encouraging results in recent trials, individuals with relapsed/refractory MCL are now experiencing clinical benefit from the noncovalent BTK inhibitor pirtrobrutinib. Investigational bispecific antibody (bsAb) therapy awaits in the wings. 

Similarly, both younger and older patients with treatment naïve MCL could soon see improvement from the addition of BTK inhibitors to each age group’s standard treatment option. The following is a description of recent developments and their potential implications for practice.  

One of the most exciting developments is the US Food and Drug Administration’s accelerated approval of pirtrobrutinib. A noncovalent BTK inhibitor, pirtrobrutinib has been found to have activity in individuals with MCL who have failed on multiple therapies, including standard BTK inhibitors. Pirtrobrutinib targets certain mutations in the BTK protein that are associated with resistance to covalent BTK inhibitors. In addition to resistance, some patients discontinue treatment with non-reversible BTK inhibitors because of intolerable toxicity. 

Approval of pirtrobrutinib was based on an evaluation involving 120 individuals (median age 71) who were previously treated with a non-reversible BTK inhibitor. Two-thirds were previously treated with ibrutinib; 30% with acalabrutinib, and 8% zanubrutinib (some received more than one BTK inhibitor previously). The vast majority (83%) discontinued treatment due to refractory or progressive disease; 10% stopped due to toxicity; and the remainder halted treatment for other reasons. 

Six in every 10 of the participants were classified on the MCL International Prognostic Index as intermediate; one-fourth were classified as high; and the remainder low. Patients received 200 mg of pirtrobrutinib once a day until disease either progressed or they experienced intolerable toxicity. Among the results:

• Overall response rate was 50%; 13% responded completely

• Median duration of response was 8.3 months

• Duration of response rate at 6 months was 65%

• Grade 3 or 4 abnormalities experienced by 10% or more of participants included decreased neutrophil counts, lymphocyte counts, and platelet counts

Further, bsAb therapy targeting CD20-CD3 is not yet approved but is showing promise as a potential therapy following BTK inhibitor failure. The treatment consists of an antibody containing two prongs. One is a CD20 protein that attaches to the lymphoma cell. The other is an anti-CD3 antibody that attaches to the T cell to bring the patient’s own T cells closer to the lymphoma to increase the cell kill. 

Preliminary studies evaluating bsAbs in individuals with MCL, many of whom have failed on multiple other types of therapies, show a remarkably high response rate. In one such investigation, the bsAb glofitamab was given to 21 individuals as monotherapy following pretreatment with obinutuzumab. The regimen produced an overall response rate of 81% (n = 17) and a complete response rate of 68% (n = 14). Response was similar in participants who had and had not received prior BTK therapy. Among those who achieved a complete response, median duration was 2.4 months, and 12 of those who reached a complete response were still in remission at the study’s data cutoff point. 

For younger individuals with treatment-naïve MCL, the current standard is chemotherapy and autologous stem-cell transplant (ASCT). For older individuals the standard is chemoimmunotherapy. The replacement or addition of the BTK inhibitor ibrutinib to these regimens is showing the promise of added clinical benefit in both age contingents. 

Investigators presented results of the three-arm TRIANGLE trial at the 64th ASH Annual Meeting in December 2022. The study compared 1) chemotherapy followed by ASCT; 2) ibrutinib plus chemotherapy followed by ASCT and ibrutinib maintenance; and 3) ibrutinib plus chemotherapy followed by ibrutinib maintenance. Participants (n = 870) ≤ 65 years of age (median age 57) with previously untreated advanced-stage MCL were randomized to 1 of the 3 regimens. Investigators looked at overall response, complete response, and failure-free survival rates (FFS). Among the results: 

• Overall response rates were 98% in the 2 groups whose treatments included ibrutinib, versus 94% in the chemotherapy followed by ASCT group. 

• Complete response rates were 45% and 36%, respectively.

• The non-ibrutinib regimen did not attain FFS superiority over ibrutinib plus chemotherapy, with a 3-year FFS rate of 72% and 86%, respectively (p=0.9979, hazard ratio [HR]: 1.77).

• Ibrutinib plus chemotherapy was shown to be superior to chemotherapy/ASCT, with a 3-year FFS rate of 88% and 72%, respectively (p=0.0008, HR: 0.52).

• The only adverse event differences of note occurred during maintenance treatment; there were significantly more grade 3-5 adverse events in the ibrutinib/chemotherapy/ASCT group, compared with the other 2 contingents.

Researchers noted in materials accompanying their presentation that, “It has been clearly demonstrated that the current standard high-dose regimen is not superior to the new ibrutinib-containing regimen without ASCT. More follow-up is needed to clarify the role of ASCT in the context of ibrutinib-containing treatment. However, the current results already support the use of ibrutinib in the first-line treatment of younger MCL patients.”

It also appears that ibrutinib added to standard chemoimmunotherapy can improve outcomes in older individuals with treatment-naïve MCL. In 2022, researchers published results from the international, randomized, double-blind, phase 3 SHINE trial. Participants (n = 523) were ≥ 65 years of age with previously untreated MCL and were randomized to receive either ibrutinib 560 mg daily or placebo added to chemoimmunotherapy consisting of bendamustine and rituximab every 4 weeks for 6 cycles. Individuals with a partial or complete response continued treatment every 8 weeks for up to 12 more doses. Investigators looked primarily at progression-free survival (PFS), as well as complete response, undetectable minimal residual disease, and time to worsening. Among the results: 

• 116 participants (44%) in the ibrutinib group experienced disease progression or died, compared with 152 (58%) in the placebo contingent. 

• Median PFS was 80.6 months and 52.9 months, respectively.

• PFS benefit was seen across most subgroups (patients categorized as high risk, and those with TP53 mutations did not benefit).

• Complete response was seen in 66% and 58% of participants, respectively.

• Undetectable minimal residual disease was observed in 62% and 57%, respectively.

• Deaths attributed to disease progression or adverse events occurred in 22% and 28%, respectively.

• Grade 3 or 4 adverse event incident rates were 82% and 77%, respectively.

Researchers noted that, “Given the shorter progression-free survival with current standard-care chemoimmunotherapy options, a prolongation of progression-free survival in response to primary therapy may provide patients with an improved opportunity for durable disease control in order to prevent or delay relapse.”

Data on the use of other BTK inhibitors as first-line treatment for MCL are forthcoming, including: 

• ECHO, a phase 3 trial assessing the efficacy of acalabrutinib versus placebo added to bendamustine and rituximab.

• MANGROVE, a phase 3 study comparing zanubrutinib plus rituximab versus bendamustine plus rituximab.

• ENRICH, a phase 2 study evaluating a chemotherapy-free option–ibrutinib and rituximab in older individuals.

• OASIS, a randomized, phase 2 trial comparing ibrutinib/anti-CD20 antibodies (Ab) and Ibrutinib/anti-CD20 Ab/venetoclax given as fixed duration combinations. 

The evolution of BTK inhibitors for relapsed MCL has great potential; further benefits continue to be explored.

The U.S. Food and Drug Administration approved epcoritamab-bysp (Epkinly, AbbVie and Genmab) today for adults with relapsed/refractory diffuse large B-cell lymphoma following at least two lines of systemic therapy. This includes patients with DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma.

Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.

“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.

A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.

The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.

Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.

At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.

The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.

Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.

The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).

The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.

The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
 

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

The U.S. Food and Drug Administration approved epcoritamab-bysp (Epkinly, AbbVie and Genmab) today for adults with relapsed/refractory diffuse large B-cell lymphoma following at least two lines of systemic therapy. This includes patients with DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma.

Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.

“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.

A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.

The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.

Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.

At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.

The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.

Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.

The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).

The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.

The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
 

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

The U.S. Food and Drug Administration approved epcoritamab-bysp (Epkinly, AbbVie and Genmab) today for adults with relapsed/refractory diffuse large B-cell lymphoma following at least two lines of systemic therapy. This includes patients with DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma.

Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.

“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.

A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.

The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.

Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.

At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.

The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.

Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.

The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).

The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.

The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
 

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

PHOENIX – Marijuana users have an almost four times greater risk of developing peripheral artery disease, compared with nonusers, results of a study of more than 600,000 marijuana users suggest, although there was no greater risk of death from myocardial infarction or other cardiac causes or need for revascularization.

Instants/Getty Images

The researchers noted, however, that the study population was young, with an average age of 37.4 years, and that the study period, from 2016 to 2019, predates the legalization of recreational marijuana in a number of states.

Nonetheless, even in this young study population, marijuana users’ risk of developing peripheral artery disease (PAD) was 3.68 times greater (P < .001) than that of nonusers. PAD at a young age could precede worse outcomes later in life, the study authors said.

“Basically, marijuana users were at increased risk of being diagnosed with peripheral artery disease, but there was no increased risk for them requiring any intervention, such as a peripheral vascular intervention, nor were they at increased risk of death from what we found,” said Hirva Vyas, DO, an internal medicine resident at Hackensack University Medical Center in New Jersey, who presented the results at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

The study used data on 623,768 marijuana users from the National Inpatient Sample, a nationwide database of inpatient visits covered by all public and commercial payers, then extracted a diagnosis for PAD from all 30 million–plus patient encounters to compare PAD rates between marijuana users and nonusers. Marijuana users were more likely to be White and to have elective rather than emergency admissions (P < .001). The researchers used diagnostic codes to identify marijuana users and PAD patients.

Recreational marijuana is legal in 22 states and the District of Columbia, according to ProCon.org. Since 2019, the last year of the study, 11 states have legalized marijuana for recreational use. “It’s a data point that we studied at one point in time, only from 2016 to 2019,” Dr. Vyas said in an interview.

“As we’ve seen over the past 4-5 years, legalization has skyrocketed and recreational use has become more and more favorable not only among younger folks but older folks,” study coauthor Harsh Jain, MD, a second-year internal medicine resident at Montefiore Medical Center in New York, said in the interview. “It would be really refreshing to see how these data change as we look at endpoints from 2019 to 2023.”

Because of the young age of the study population, Dr. Jain said, these findings may not accurately represent the true cardiovascular risks of marijuana use, especially later in life.

“One of the biggest secondary endpoints that we wanted to study was the development of chronic conditions that lead to multiple rehospitalizations, the most significant one of which would be the development of heart failure,” Dr. Jain said. “However, it was difficult to stratify because, again, many of these patients were very young and so they did not carry the diagnosis for heart failure, so we couldn’t complete that subset analysis.”

The goal is to extend the study period out to 2023, Dr. Jain said. “We know that these are very crude and rudimentary data findings that we presented so far, but we’re hoping that the final paper gives us a chance to flesh out all the details of our study and also gives us a chance to expand going forward,” he said.

The findings are in line with other research into the effects of marijuana and cardiovascular disease, said Carl “Chip” Lavie, MD, medical director for cardiac rehabilitation and prevention at the John Ochsner Heart and Vascular Institute in New Orleans who’s published a number of studies on PAD and substance use, including marijuana.

“It is known that cannabis is associated with more vasoconstriction, has sympathomimetic effects, causes endothelial dysfunction and increased platelet aggregation, and is known to increase the risk of acute myocardial infarction, especially in the hour or so after use,” he said in written comments sent to this news organization.

“It is also well known to be a cause of thromboangiitis obliterans, which is in the PAD family,” he added. “Based on these mechanisms, one would expect an increased PAD and, especially, PAD events. The 3.7-fold increased risk is supportive of this increased PAD.”

One study strength, Dr. Lavie pointed out, is that it’s one of the few studies that found an association between marijuana and PAD, which hasn’t been studied as well as other cardiovascular endpoints. “However,” he said, “the limitation is this is just an inpatient sample, and it is all based on coding – e.g., a patient could have PAD and it may not have been coded.”

PHOENIX – Marijuana users have an almost four times greater risk of developing peripheral artery disease, compared with nonusers, results of a study of more than 600,000 marijuana users suggest, although there was no greater risk of death from myocardial infarction or other cardiac causes or need for revascularization.

Instants/Getty Images

The researchers noted, however, that the study population was young, with an average age of 37.4 years, and that the study period, from 2016 to 2019, predates the legalization of recreational marijuana in a number of states.

Nonetheless, even in this young study population, marijuana users’ risk of developing peripheral artery disease (PAD) was 3.68 times greater (P < .001) than that of nonusers. PAD at a young age could precede worse outcomes later in life, the study authors said.

“Basically, marijuana users were at increased risk of being diagnosed with peripheral artery disease, but there was no increased risk for them requiring any intervention, such as a peripheral vascular intervention, nor were they at increased risk of death from what we found,” said Hirva Vyas, DO, an internal medicine resident at Hackensack University Medical Center in New Jersey, who presented the results at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

The study used data on 623,768 marijuana users from the National Inpatient Sample, a nationwide database of inpatient visits covered by all public and commercial payers, then extracted a diagnosis for PAD from all 30 million–plus patient encounters to compare PAD rates between marijuana users and nonusers. Marijuana users were more likely to be White and to have elective rather than emergency admissions (P < .001). The researchers used diagnostic codes to identify marijuana users and PAD patients.

Recreational marijuana is legal in 22 states and the District of Columbia, according to ProCon.org. Since 2019, the last year of the study, 11 states have legalized marijuana for recreational use. “It’s a data point that we studied at one point in time, only from 2016 to 2019,” Dr. Vyas said in an interview.

“As we’ve seen over the past 4-5 years, legalization has skyrocketed and recreational use has become more and more favorable not only among younger folks but older folks,” study coauthor Harsh Jain, MD, a second-year internal medicine resident at Montefiore Medical Center in New York, said in the interview. “It would be really refreshing to see how these data change as we look at endpoints from 2019 to 2023.”

Because of the young age of the study population, Dr. Jain said, these findings may not accurately represent the true cardiovascular risks of marijuana use, especially later in life.

“One of the biggest secondary endpoints that we wanted to study was the development of chronic conditions that lead to multiple rehospitalizations, the most significant one of which would be the development of heart failure,” Dr. Jain said. “However, it was difficult to stratify because, again, many of these patients were very young and so they did not carry the diagnosis for heart failure, so we couldn’t complete that subset analysis.”

The goal is to extend the study period out to 2023, Dr. Jain said. “We know that these are very crude and rudimentary data findings that we presented so far, but we’re hoping that the final paper gives us a chance to flesh out all the details of our study and also gives us a chance to expand going forward,” he said.

The findings are in line with other research into the effects of marijuana and cardiovascular disease, said Carl “Chip” Lavie, MD, medical director for cardiac rehabilitation and prevention at the John Ochsner Heart and Vascular Institute in New Orleans who’s published a number of studies on PAD and substance use, including marijuana.

“It is known that cannabis is associated with more vasoconstriction, has sympathomimetic effects, causes endothelial dysfunction and increased platelet aggregation, and is known to increase the risk of acute myocardial infarction, especially in the hour or so after use,” he said in written comments sent to this news organization.

“It is also well known to be a cause of thromboangiitis obliterans, which is in the PAD family,” he added. “Based on these mechanisms, one would expect an increased PAD and, especially, PAD events. The 3.7-fold increased risk is supportive of this increased PAD.”

One study strength, Dr. Lavie pointed out, is that it’s one of the few studies that found an association between marijuana and PAD, which hasn’t been studied as well as other cardiovascular endpoints. “However,” he said, “the limitation is this is just an inpatient sample, and it is all based on coding – e.g., a patient could have PAD and it may not have been coded.”

PHOENIX – Marijuana users have an almost four times greater risk of developing peripheral artery disease, compared with nonusers, results of a study of more than 600,000 marijuana users suggest, although there was no greater risk of death from myocardial infarction or other cardiac causes or need for revascularization.

Instants/Getty Images

The researchers noted, however, that the study population was young, with an average age of 37.4 years, and that the study period, from 2016 to 2019, predates the legalization of recreational marijuana in a number of states.

Nonetheless, even in this young study population, marijuana users’ risk of developing peripheral artery disease (PAD) was 3.68 times greater (P < .001) than that of nonusers. PAD at a young age could precede worse outcomes later in life, the study authors said.

“Basically, marijuana users were at increased risk of being diagnosed with peripheral artery disease, but there was no increased risk for them requiring any intervention, such as a peripheral vascular intervention, nor were they at increased risk of death from what we found,” said Hirva Vyas, DO, an internal medicine resident at Hackensack University Medical Center in New Jersey, who presented the results at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.

The study used data on 623,768 marijuana users from the National Inpatient Sample, a nationwide database of inpatient visits covered by all public and commercial payers, then extracted a diagnosis for PAD from all 30 million–plus patient encounters to compare PAD rates between marijuana users and nonusers. Marijuana users were more likely to be White and to have elective rather than emergency admissions (P < .001). The researchers used diagnostic codes to identify marijuana users and PAD patients.

Recreational marijuana is legal in 22 states and the District of Columbia, according to ProCon.org. Since 2019, the last year of the study, 11 states have legalized marijuana for recreational use. “It’s a data point that we studied at one point in time, only from 2016 to 2019,” Dr. Vyas said in an interview.

“As we’ve seen over the past 4-5 years, legalization has skyrocketed and recreational use has become more and more favorable not only among younger folks but older folks,” study coauthor Harsh Jain, MD, a second-year internal medicine resident at Montefiore Medical Center in New York, said in the interview. “It would be really refreshing to see how these data change as we look at endpoints from 2019 to 2023.”

Because of the young age of the study population, Dr. Jain said, these findings may not accurately represent the true cardiovascular risks of marijuana use, especially later in life.

“One of the biggest secondary endpoints that we wanted to study was the development of chronic conditions that lead to multiple rehospitalizations, the most significant one of which would be the development of heart failure,” Dr. Jain said. “However, it was difficult to stratify because, again, many of these patients were very young and so they did not carry the diagnosis for heart failure, so we couldn’t complete that subset analysis.”

The goal is to extend the study period out to 2023, Dr. Jain said. “We know that these are very crude and rudimentary data findings that we presented so far, but we’re hoping that the final paper gives us a chance to flesh out all the details of our study and also gives us a chance to expand going forward,” he said.

The findings are in line with other research into the effects of marijuana and cardiovascular disease, said Carl “Chip” Lavie, MD, medical director for cardiac rehabilitation and prevention at the John Ochsner Heart and Vascular Institute in New Orleans who’s published a number of studies on PAD and substance use, including marijuana.

“It is known that cannabis is associated with more vasoconstriction, has sympathomimetic effects, causes endothelial dysfunction and increased platelet aggregation, and is known to increase the risk of acute myocardial infarction, especially in the hour or so after use,” he said in written comments sent to this news organization.

“It is also well known to be a cause of thromboangiitis obliterans, which is in the PAD family,” he added. “Based on these mechanisms, one would expect an increased PAD and, especially, PAD events. The 3.7-fold increased risk is supportive of this increased PAD.”

One study strength, Dr. Lavie pointed out, is that it’s one of the few studies that found an association between marijuana and PAD, which hasn’t been studied as well as other cardiovascular endpoints. “However,” he said, “the limitation is this is just an inpatient sample, and it is all based on coding – e.g., a patient could have PAD and it may not have been coded.”

Real-world data accumulated in Europe outside of a clinical trial support both the safety and the benefit of two transcatheter edge-to-edge (TEER) devices designed specifically for the treatment of tricuspid regurgitation (TR).

For the TriClip system (Abbott), the data were drawn from a prospective postmarketing registry, and for the EVOQUE system (Edwards Lifesciences), data were generated by a compassionate use program.

The TriClip system is approved and available in Europe, but neither system has regulatory approval in the United States.

The two sets of data, each presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, are consistent with controlled trials. Each system was associated with high rates of procedural success, low rates of adverse events, and sustained improvements in quality of life.
 

Real-world backup for TRILUMINATE

Presented just days before the pivotal multinational TRILUMINATE trial was published in the New England Journal of Medicine, the bRIGHT postmarketing study of the TriClip device demonstrated a procedural rate of success and a subsequent reduction in TR that was at least as good but in a substantially sicker patient population.

“To appreciate these results, you have to put into perspective the baseline TR in our population,” reported Philipp Lurz, MD, PhD, of the Heart Center Leipzig, University of Leipzig, Germany. Whereas only 70% of those randomized in TRILUMINATE had grade 4 (massive) or 5 (torrential) TR, the proportion was 90% in bRIGHT.

The proportion with TR of moderate or less severity was 77% when assessed at 30 days in bRIGHT versus 72%, however, when assessed at 1 year in TRILUMINATE. In addition, procedural success was 99% in both studies even though patients in bRIGHT were on average older and had more comorbidities. At baseline, 80% of bRIGHT patients were in New York Heart Association (NYHA) class III or IV heart failure versus 59% of those in TRILUMINATE.

TRILUMINATE data, presented prior to publication at the annual meeting of the American College of Cardiology earlier this year, did not associate the transcatheter TR repair with a reduction in mortality or a reduction in hospitalization for heart failure, which were the first two of three hierarchical endpoints, but it did show benefit on the third, which was quality of life. As measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), patients in the transcatheter repair group gained 12.3 points versus 0.6 points (P < .001) on medical therapy.

In the bRIGHT registry, patients gained 19 points in the KCCQ score after treatment. By 30 days, the proportion of patients in NHYA class III/IV had fallen from 80% to 20%. The major adverse event rate of 2.5% at 30 days was only modestly higher than the 1.7% rate at 30 days in TRILUMINATE.

“The safety profile remained strong despite the sicker population treated in the registry,” reported Dr. Lurz, whose results were simultaneously published in the Journal of the American College of Cardiology (JACC).

The bRIGHT registry analysis was based on 511 patients treated at 26 sites in Europe. Dr. Lurz characterized it as “the first prospective, single-arm, open-label, multicenter, postmarket registry to evaluate the safety and performance of any transcatheter tricuspid valve repair system.”

In a panel discussion following the presentation, Nicole Karam, MD, PhD, codirector of the heart valve unit, Hospital Georges Pompidou, Paris, praised a study of TEER tricuspid valve device in the real world, but she pointed out that the question of who to treat remains unanswered. Although symptom relief has value for a condition that can impose large deficits in quality of life, she called for more data to identify optimal candidates, particularly in the persistent absence of a major effect on hard endpoints.

Dr. Lurz agreed. In bRIGHT, predictors of a moderate or less TR at discharge included a smaller tethering distance, a smaller right ventricular end diastolic dimension, a smaller right atrial volume, and a smaller tricuspid annular diameter.

Each of these predictors argues for earlier treatment, he said, even if later treatment in a clinical trial provides a greater likelihood of eventually demonstrating benefits on hard endpoints.

‘Remarkable reduction’

The data from the much smaller compassionate use evaluation of the EVOQUE system generated similar evidence of safety and benefit while also making the point that earlier intervention offers a greater opportunity for preventing irreversible progression. With much longer follow up, the compassionate-use analysis, which involved patients even sicker than those included in bRIGHT, suggested these repairs are durable.

In this retrospective analysis of 38 patients treated at eight centers in Europe, the United States, and Canada, the mortality climbed steadily over 2 years of follow-up, reaching 29% at 2 years despite the fact that TR was reduced to < 1% after the procedure and remained durably suppressed at a median follow-up of 520 days.

The tricuspid valve repair with the EVOQUE system “was associated with a remarkable reduction in heart failure symptoms and significant improvement in NYHA functional class up to a maximum of 1,074 days after the intervention,” reported Lukas Stolz, MD, an interventional cardiologist at Ludwig-Maximilians-University, Munich.

In the data he presented at EuroPCR, which was published simultaneously as a letter in JACC, he said that favorable reverse remodeling of the right ventricle, which was observed as early as 30 days after the procedure, was maintained at long-term follow up.

The uncontrolled data from the compassionate analysis, like the bRIGHT registry, could not confirm that tricuspid valve repair changes the trajectory of progressive heart disease, but the favorable effects Dr. Stolz reported on cardiovascular function, not just symptoms, support this idea.

Dr. Lutz has financial relationships with Edwards Lifesciences, ReCor, and Abbott, which funded the bRIGHT registry. Dr. Karam reports financial relationships with Abbott, Edwards Lifesciences, and Medtronic. Dr. Stolz reports no potential conflicts of interest, but other coinvestigators of the retrospective analysis have financial relationships with Edwards Lifesciences, which is developing the EVOQUE system.

Real-world data accumulated in Europe outside of a clinical trial support both the safety and the benefit of two transcatheter edge-to-edge (TEER) devices designed specifically for the treatment of tricuspid regurgitation (TR).

For the TriClip system (Abbott), the data were drawn from a prospective postmarketing registry, and for the EVOQUE system (Edwards Lifesciences), data were generated by a compassionate use program.

The TriClip system is approved and available in Europe, but neither system has regulatory approval in the United States.

The two sets of data, each presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, are consistent with controlled trials. Each system was associated with high rates of procedural success, low rates of adverse events, and sustained improvements in quality of life.
 

Real-world backup for TRILUMINATE

Presented just days before the pivotal multinational TRILUMINATE trial was published in the New England Journal of Medicine, the bRIGHT postmarketing study of the TriClip device demonstrated a procedural rate of success and a subsequent reduction in TR that was at least as good but in a substantially sicker patient population.

“To appreciate these results, you have to put into perspective the baseline TR in our population,” reported Philipp Lurz, MD, PhD, of the Heart Center Leipzig, University of Leipzig, Germany. Whereas only 70% of those randomized in TRILUMINATE had grade 4 (massive) or 5 (torrential) TR, the proportion was 90% in bRIGHT.

The proportion with TR of moderate or less severity was 77% when assessed at 30 days in bRIGHT versus 72%, however, when assessed at 1 year in TRILUMINATE. In addition, procedural success was 99% in both studies even though patients in bRIGHT were on average older and had more comorbidities. At baseline, 80% of bRIGHT patients were in New York Heart Association (NYHA) class III or IV heart failure versus 59% of those in TRILUMINATE.

TRILUMINATE data, presented prior to publication at the annual meeting of the American College of Cardiology earlier this year, did not associate the transcatheter TR repair with a reduction in mortality or a reduction in hospitalization for heart failure, which were the first two of three hierarchical endpoints, but it did show benefit on the third, which was quality of life. As measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), patients in the transcatheter repair group gained 12.3 points versus 0.6 points (P < .001) on medical therapy.

In the bRIGHT registry, patients gained 19 points in the KCCQ score after treatment. By 30 days, the proportion of patients in NHYA class III/IV had fallen from 80% to 20%. The major adverse event rate of 2.5% at 30 days was only modestly higher than the 1.7% rate at 30 days in TRILUMINATE.

“The safety profile remained strong despite the sicker population treated in the registry,” reported Dr. Lurz, whose results were simultaneously published in the Journal of the American College of Cardiology (JACC).

The bRIGHT registry analysis was based on 511 patients treated at 26 sites in Europe. Dr. Lurz characterized it as “the first prospective, single-arm, open-label, multicenter, postmarket registry to evaluate the safety and performance of any transcatheter tricuspid valve repair system.”

In a panel discussion following the presentation, Nicole Karam, MD, PhD, codirector of the heart valve unit, Hospital Georges Pompidou, Paris, praised a study of TEER tricuspid valve device in the real world, but she pointed out that the question of who to treat remains unanswered. Although symptom relief has value for a condition that can impose large deficits in quality of life, she called for more data to identify optimal candidates, particularly in the persistent absence of a major effect on hard endpoints.

Dr. Lurz agreed. In bRIGHT, predictors of a moderate or less TR at discharge included a smaller tethering distance, a smaller right ventricular end diastolic dimension, a smaller right atrial volume, and a smaller tricuspid annular diameter.

Each of these predictors argues for earlier treatment, he said, even if later treatment in a clinical trial provides a greater likelihood of eventually demonstrating benefits on hard endpoints.

‘Remarkable reduction’

The data from the much smaller compassionate use evaluation of the EVOQUE system generated similar evidence of safety and benefit while also making the point that earlier intervention offers a greater opportunity for preventing irreversible progression. With much longer follow up, the compassionate-use analysis, which involved patients even sicker than those included in bRIGHT, suggested these repairs are durable.

In this retrospective analysis of 38 patients treated at eight centers in Europe, the United States, and Canada, the mortality climbed steadily over 2 years of follow-up, reaching 29% at 2 years despite the fact that TR was reduced to < 1% after the procedure and remained durably suppressed at a median follow-up of 520 days.

The tricuspid valve repair with the EVOQUE system “was associated with a remarkable reduction in heart failure symptoms and significant improvement in NYHA functional class up to a maximum of 1,074 days after the intervention,” reported Lukas Stolz, MD, an interventional cardiologist at Ludwig-Maximilians-University, Munich.

In the data he presented at EuroPCR, which was published simultaneously as a letter in JACC, he said that favorable reverse remodeling of the right ventricle, which was observed as early as 30 days after the procedure, was maintained at long-term follow up.

The uncontrolled data from the compassionate analysis, like the bRIGHT registry, could not confirm that tricuspid valve repair changes the trajectory of progressive heart disease, but the favorable effects Dr. Stolz reported on cardiovascular function, not just symptoms, support this idea.

Dr. Lutz has financial relationships with Edwards Lifesciences, ReCor, and Abbott, which funded the bRIGHT registry. Dr. Karam reports financial relationships with Abbott, Edwards Lifesciences, and Medtronic. Dr. Stolz reports no potential conflicts of interest, but other coinvestigators of the retrospective analysis have financial relationships with Edwards Lifesciences, which is developing the EVOQUE system.

Real-world data accumulated in Europe outside of a clinical trial support both the safety and the benefit of two transcatheter edge-to-edge (TEER) devices designed specifically for the treatment of tricuspid regurgitation (TR).

For the TriClip system (Abbott), the data were drawn from a prospective postmarketing registry, and for the EVOQUE system (Edwards Lifesciences), data were generated by a compassionate use program.

The TriClip system is approved and available in Europe, but neither system has regulatory approval in the United States.

The two sets of data, each presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, are consistent with controlled trials. Each system was associated with high rates of procedural success, low rates of adverse events, and sustained improvements in quality of life.
 

Real-world backup for TRILUMINATE

Presented just days before the pivotal multinational TRILUMINATE trial was published in the New England Journal of Medicine, the bRIGHT postmarketing study of the TriClip device demonstrated a procedural rate of success and a subsequent reduction in TR that was at least as good but in a substantially sicker patient population.

“To appreciate these results, you have to put into perspective the baseline TR in our population,” reported Philipp Lurz, MD, PhD, of the Heart Center Leipzig, University of Leipzig, Germany. Whereas only 70% of those randomized in TRILUMINATE had grade 4 (massive) or 5 (torrential) TR, the proportion was 90% in bRIGHT.

The proportion with TR of moderate or less severity was 77% when assessed at 30 days in bRIGHT versus 72%, however, when assessed at 1 year in TRILUMINATE. In addition, procedural success was 99% in both studies even though patients in bRIGHT were on average older and had more comorbidities. At baseline, 80% of bRIGHT patients were in New York Heart Association (NYHA) class III or IV heart failure versus 59% of those in TRILUMINATE.

TRILUMINATE data, presented prior to publication at the annual meeting of the American College of Cardiology earlier this year, did not associate the transcatheter TR repair with a reduction in mortality or a reduction in hospitalization for heart failure, which were the first two of three hierarchical endpoints, but it did show benefit on the third, which was quality of life. As measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), patients in the transcatheter repair group gained 12.3 points versus 0.6 points (P < .001) on medical therapy.

In the bRIGHT registry, patients gained 19 points in the KCCQ score after treatment. By 30 days, the proportion of patients in NHYA class III/IV had fallen from 80% to 20%. The major adverse event rate of 2.5% at 30 days was only modestly higher than the 1.7% rate at 30 days in TRILUMINATE.

“The safety profile remained strong despite the sicker population treated in the registry,” reported Dr. Lurz, whose results were simultaneously published in the Journal of the American College of Cardiology (JACC).

The bRIGHT registry analysis was based on 511 patients treated at 26 sites in Europe. Dr. Lurz characterized it as “the first prospective, single-arm, open-label, multicenter, postmarket registry to evaluate the safety and performance of any transcatheter tricuspid valve repair system.”

In a panel discussion following the presentation, Nicole Karam, MD, PhD, codirector of the heart valve unit, Hospital Georges Pompidou, Paris, praised a study of TEER tricuspid valve device in the real world, but she pointed out that the question of who to treat remains unanswered. Although symptom relief has value for a condition that can impose large deficits in quality of life, she called for more data to identify optimal candidates, particularly in the persistent absence of a major effect on hard endpoints.

Dr. Lurz agreed. In bRIGHT, predictors of a moderate or less TR at discharge included a smaller tethering distance, a smaller right ventricular end diastolic dimension, a smaller right atrial volume, and a smaller tricuspid annular diameter.

Each of these predictors argues for earlier treatment, he said, even if later treatment in a clinical trial provides a greater likelihood of eventually demonstrating benefits on hard endpoints.

‘Remarkable reduction’

The data from the much smaller compassionate use evaluation of the EVOQUE system generated similar evidence of safety and benefit while also making the point that earlier intervention offers a greater opportunity for preventing irreversible progression. With much longer follow up, the compassionate-use analysis, which involved patients even sicker than those included in bRIGHT, suggested these repairs are durable.

In this retrospective analysis of 38 patients treated at eight centers in Europe, the United States, and Canada, the mortality climbed steadily over 2 years of follow-up, reaching 29% at 2 years despite the fact that TR was reduced to < 1% after the procedure and remained durably suppressed at a median follow-up of 520 days.

The tricuspid valve repair with the EVOQUE system “was associated with a remarkable reduction in heart failure symptoms and significant improvement in NYHA functional class up to a maximum of 1,074 days after the intervention,” reported Lukas Stolz, MD, an interventional cardiologist at Ludwig-Maximilians-University, Munich.

In the data he presented at EuroPCR, which was published simultaneously as a letter in JACC, he said that favorable reverse remodeling of the right ventricle, which was observed as early as 30 days after the procedure, was maintained at long-term follow up.

The uncontrolled data from the compassionate analysis, like the bRIGHT registry, could not confirm that tricuspid valve repair changes the trajectory of progressive heart disease, but the favorable effects Dr. Stolz reported on cardiovascular function, not just symptoms, support this idea.

Dr. Lutz has financial relationships with Edwards Lifesciences, ReCor, and Abbott, which funded the bRIGHT registry. Dr. Karam reports financial relationships with Abbott, Edwards Lifesciences, and Medtronic. Dr. Stolz reports no potential conflicts of interest, but other coinvestigators of the retrospective analysis have financial relationships with Edwards Lifesciences, which is developing the EVOQUE system.

DUBLIN – Substantial reductions in body weight across body mass index categories, as well as improved body composition, were achieved with tirzepatide (Mounjaro) in adults for chronic weight management, according to the latest results of the SURMOUNT-1 study.

The new analysis showed that up to 63% of participants achieved a reduction in body weight of at least 20%, and all three tirzepatide doses (5 mg, 10 mg, and 15 mg) led to substantial, clinically meaningful, and sustained body-weight reduction, compared with placebo at 72 weeks of follow-up.

Mean weight loss was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for placebo (all P < .001 vs. placebo). And among participants taking the highest 15-mg dose of tirzepatide, 96%, 90%, and 78% of patients achieved weight reductions of at least 5%, 10%, and 15%.

Tirzepatide is approved in the United States and the European Union for the treatment of type 2 diabetes but is not yet approved for obesity in any country. The manufacturer of tirzepatide, Eli Lilly, intends to seek approval for the drug as an obesity treatment from the U.S. Food and Drug Administration, European Medicines Agency, and in other territories beginning in 2023.

Regardless of baseline BMI category, 9 out of 10 people achieved the greater than or equal to 5% body weight reduction threshold across all doses of tirzepatide, and at the higher doses, over one-third achieved weight loss of 25% or more.

“Similar to lifestyle and surgical treatments, participants on tirzepatide had around a threefold greater percent reduction in fat mass, compared with lean mass, resulting in an overall improvement in body composition,” reported SURMOUNT-1 co-investigator Louis Aronne, MD, Comprehensive Weight Control Center, Weill Cornell Medicine, New York.

Weight loss and body composition explored

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works to activate the GIP and GLP-1 receptors, respectively, found in areas of the brain important for appetite regulation, decreasing food intake, and modulating fat utilization. 

The phase 3, double-blind, randomized, controlled trial included data from 2,539 adults with a BMI greater than or equal to 30 kg/m² (class I, II, III obesity) or greater than or equal to 27 kg/m² (overweight) with one or more weight-related complications, excluding diabetes. At baseline, mean body weight was 104.8 kg, mean BMI was 38.0 kg/m², and 94.5% of participants had BMI greater than or equal to 30 kg/m².

Patients were randomized to once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks. The primary objective was to show that tirzepatide was superior to placebo in terms of percentage change in body weight and proportion of participants with body-weight reduction of greater than or equal to 5%. The percentage change from baseline body weight and proportion of participants with body weight reduction greater than or equal to 5% were also assessed across BMI categories of greater than or equal to 27 to less than 30 kg/m², greater than or equal to 30 to less than 35 kg/m² (class 1 obesity), greater than or equal to 35 to less than 40 kg/m² (class 2 obesity), and greater than or equal to 40 kg/m² (class 3 obesity).

In addition, in a retrospective subanalysis, body composition was evaluated in a subpopulation that underwent dual-energy x-ray absorptiometry, assessing change from baseline body composition within age subgroups less than 50 years (n = 99), 50-64.9 years (n = 41), and greater than or equal to 65 years (n = 20).

The average weight reduction over the 72 weeks of follow-up was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for participants taking placebo (all P < .001 vs. placebo).

The percentages of participants reaching target weight reductions of greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, greater than or equal to 20%, and greater than or equal to 25% were recorded. Over 90% achieved greater than or equal to 5% weight loss, irrespective of BMI and tirzepatide dose, while 55.5% and 62.9% in the 10-mg and 15-mg groups achieved greater than or equal to 20% weight loss, and 35.0% and 39.7% in the 10-mg and 15-mg groups achieved greater than or equal to 25% weight loss, respectively.

By increasing BMI category, in the 10-mg group, weight loss was –18.2 kg, –21.9 kg, –22.0, and –20.7 kg; and in the 15-mg group, weight loss was –18.1kg, –21.2 kg, –24.5 kg, and –22.8 kg. Weight loss in the 5-mg group ranged from –16.6 kg to –15.9 kg from lowest to highest BMI category. 

“In the lower-weight categories, there is less weight to lose, so we see a flattening of the curve [with a] maximum of around 18%, so it may be that as we learn more about a drug that is so potent, we recognize that we don’t need to use such a high dose in people with BMI 27-30 kg/m²,” he explained. “It’s the higher BMI categories where we need the higher dose.”

As with lifestyle and surgical treatments, participants taking tirzepatide had around a three times greater percentage reduction in fat mass than lean mass, resulting in an overall improvement in body composition, reported Dr. Aronne.

“We want loss of fat, not lean mass, and we know that we lose around one part lean to three parts fat mass when on a diet and exercise regimen,” he went on to explain. “We see exactly this [balance of lean-to-fat-mass loss] here with 33.9% total fat mass reduction in the treatment group, compared with 8.2% in the placebo group.”

Visceral fat mass reduction was 40% in the treatment group, compared with 7.3% with placebo. “It’s good to see there’s more loss of visceral fat,” said Dr. Aronne. Lean mass loss was 10.9%. “So around three times greater reduction in fat over lean mass loss, resulting in overall improvement of body composition,” he reported. 

Also, in older people (≥ 65 years) there was approximately no difference in fat versus lean mass loss, compared with younger people, despite older people being more likely to lose more lean mass.

With respect to patient-reported outcomes based on the 36-item Short-Form Health Survey (SF-36), Dr. Aronne said that physical functioning scores significantly improved at 72 weeks, compared with placebo, particularly in participants with physical function limitations at baseline.

“In an interesting subanalysis, those with physical limitations at baseline showed a significant improvement versus placebo of over 5% difference [considered significant],” he added.

Safety and tolerability were previously reported in the NEJM article. The most common adverse events with tirzepatide were gastrointestinal, and adverse events causing treatment discontinuation occurred in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg doses or placebo, respectively.

“A revolution is coming in the treatment of obesity and cardiometabolic disease, and most physicians cannot grasp this. We’re finally getting the efficacy we’ve been looking for that will produce benefits in every realm,” concluded Dr. Aronne. “These data show that we are now hitting all the secondary endpoints and making our patients better.”

“I think this bodes well. I always envisioned a time when the treatment of obesity would come first before the treatment of cardiometabolic complications of obesity, and I think we’re on the verge of that era with semaglutide, tirzepatide, and the very exciting treatments to come.”

The SURMOUNT-1 trial was sponsored by Lilly. Dr. Aronne is cofounder, chief scientific advisor, and a member of the board of directors for Intellihealth. He is also a paid scientific advisory board member for Eli Lilly.

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

DUBLIN – Substantial reductions in body weight across body mass index categories, as well as improved body composition, were achieved with tirzepatide (Mounjaro) in adults for chronic weight management, according to the latest results of the SURMOUNT-1 study.

The new analysis showed that up to 63% of participants achieved a reduction in body weight of at least 20%, and all three tirzepatide doses (5 mg, 10 mg, and 15 mg) led to substantial, clinically meaningful, and sustained body-weight reduction, compared with placebo at 72 weeks of follow-up.

Mean weight loss was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for placebo (all P < .001 vs. placebo). And among participants taking the highest 15-mg dose of tirzepatide, 96%, 90%, and 78% of patients achieved weight reductions of at least 5%, 10%, and 15%.

Tirzepatide is approved in the United States and the European Union for the treatment of type 2 diabetes but is not yet approved for obesity in any country. The manufacturer of tirzepatide, Eli Lilly, intends to seek approval for the drug as an obesity treatment from the U.S. Food and Drug Administration, European Medicines Agency, and in other territories beginning in 2023.

Regardless of baseline BMI category, 9 out of 10 people achieved the greater than or equal to 5% body weight reduction threshold across all doses of tirzepatide, and at the higher doses, over one-third achieved weight loss of 25% or more.

“Similar to lifestyle and surgical treatments, participants on tirzepatide had around a threefold greater percent reduction in fat mass, compared with lean mass, resulting in an overall improvement in body composition,” reported SURMOUNT-1 co-investigator Louis Aronne, MD, Comprehensive Weight Control Center, Weill Cornell Medicine, New York.

Weight loss and body composition explored

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works to activate the GIP and GLP-1 receptors, respectively, found in areas of the brain important for appetite regulation, decreasing food intake, and modulating fat utilization. 

The phase 3, double-blind, randomized, controlled trial included data from 2,539 adults with a BMI greater than or equal to 30 kg/m² (class I, II, III obesity) or greater than or equal to 27 kg/m² (overweight) with one or more weight-related complications, excluding diabetes. At baseline, mean body weight was 104.8 kg, mean BMI was 38.0 kg/m², and 94.5% of participants had BMI greater than or equal to 30 kg/m².

Patients were randomized to once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks. The primary objective was to show that tirzepatide was superior to placebo in terms of percentage change in body weight and proportion of participants with body-weight reduction of greater than or equal to 5%. The percentage change from baseline body weight and proportion of participants with body weight reduction greater than or equal to 5% were also assessed across BMI categories of greater than or equal to 27 to less than 30 kg/m², greater than or equal to 30 to less than 35 kg/m² (class 1 obesity), greater than or equal to 35 to less than 40 kg/m² (class 2 obesity), and greater than or equal to 40 kg/m² (class 3 obesity).

In addition, in a retrospective subanalysis, body composition was evaluated in a subpopulation that underwent dual-energy x-ray absorptiometry, assessing change from baseline body composition within age subgroups less than 50 years (n = 99), 50-64.9 years (n = 41), and greater than or equal to 65 years (n = 20).

The average weight reduction over the 72 weeks of follow-up was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for participants taking placebo (all P < .001 vs. placebo).

The percentages of participants reaching target weight reductions of greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, greater than or equal to 20%, and greater than or equal to 25% were recorded. Over 90% achieved greater than or equal to 5% weight loss, irrespective of BMI and tirzepatide dose, while 55.5% and 62.9% in the 10-mg and 15-mg groups achieved greater than or equal to 20% weight loss, and 35.0% and 39.7% in the 10-mg and 15-mg groups achieved greater than or equal to 25% weight loss, respectively.

By increasing BMI category, in the 10-mg group, weight loss was –18.2 kg, –21.9 kg, –22.0, and –20.7 kg; and in the 15-mg group, weight loss was –18.1kg, –21.2 kg, –24.5 kg, and –22.8 kg. Weight loss in the 5-mg group ranged from –16.6 kg to –15.9 kg from lowest to highest BMI category. 

“In the lower-weight categories, there is less weight to lose, so we see a flattening of the curve [with a] maximum of around 18%, so it may be that as we learn more about a drug that is so potent, we recognize that we don’t need to use such a high dose in people with BMI 27-30 kg/m²,” he explained. “It’s the higher BMI categories where we need the higher dose.”

As with lifestyle and surgical treatments, participants taking tirzepatide had around a three times greater percentage reduction in fat mass than lean mass, resulting in an overall improvement in body composition, reported Dr. Aronne.

“We want loss of fat, not lean mass, and we know that we lose around one part lean to three parts fat mass when on a diet and exercise regimen,” he went on to explain. “We see exactly this [balance of lean-to-fat-mass loss] here with 33.9% total fat mass reduction in the treatment group, compared with 8.2% in the placebo group.”

Visceral fat mass reduction was 40% in the treatment group, compared with 7.3% with placebo. “It’s good to see there’s more loss of visceral fat,” said Dr. Aronne. Lean mass loss was 10.9%. “So around three times greater reduction in fat over lean mass loss, resulting in overall improvement of body composition,” he reported. 

Also, in older people (≥ 65 years) there was approximately no difference in fat versus lean mass loss, compared with younger people, despite older people being more likely to lose more lean mass.

With respect to patient-reported outcomes based on the 36-item Short-Form Health Survey (SF-36), Dr. Aronne said that physical functioning scores significantly improved at 72 weeks, compared with placebo, particularly in participants with physical function limitations at baseline.

“In an interesting subanalysis, those with physical limitations at baseline showed a significant improvement versus placebo of over 5% difference [considered significant],” he added.

Safety and tolerability were previously reported in the NEJM article. The most common adverse events with tirzepatide were gastrointestinal, and adverse events causing treatment discontinuation occurred in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg doses or placebo, respectively.

“A revolution is coming in the treatment of obesity and cardiometabolic disease, and most physicians cannot grasp this. We’re finally getting the efficacy we’ve been looking for that will produce benefits in every realm,” concluded Dr. Aronne. “These data show that we are now hitting all the secondary endpoints and making our patients better.”

“I think this bodes well. I always envisioned a time when the treatment of obesity would come first before the treatment of cardiometabolic complications of obesity, and I think we’re on the verge of that era with semaglutide, tirzepatide, and the very exciting treatments to come.”

The SURMOUNT-1 trial was sponsored by Lilly. Dr. Aronne is cofounder, chief scientific advisor, and a member of the board of directors for Intellihealth. He is also a paid scientific advisory board member for Eli Lilly.

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

DUBLIN – Substantial reductions in body weight across body mass index categories, as well as improved body composition, were achieved with tirzepatide (Mounjaro) in adults for chronic weight management, according to the latest results of the SURMOUNT-1 study.

The new analysis showed that up to 63% of participants achieved a reduction in body weight of at least 20%, and all three tirzepatide doses (5 mg, 10 mg, and 15 mg) led to substantial, clinically meaningful, and sustained body-weight reduction, compared with placebo at 72 weeks of follow-up.

Mean weight loss was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for placebo (all P < .001 vs. placebo). And among participants taking the highest 15-mg dose of tirzepatide, 96%, 90%, and 78% of patients achieved weight reductions of at least 5%, 10%, and 15%.

Tirzepatide is approved in the United States and the European Union for the treatment of type 2 diabetes but is not yet approved for obesity in any country. The manufacturer of tirzepatide, Eli Lilly, intends to seek approval for the drug as an obesity treatment from the U.S. Food and Drug Administration, European Medicines Agency, and in other territories beginning in 2023.

Regardless of baseline BMI category, 9 out of 10 people achieved the greater than or equal to 5% body weight reduction threshold across all doses of tirzepatide, and at the higher doses, over one-third achieved weight loss of 25% or more.

“Similar to lifestyle and surgical treatments, participants on tirzepatide had around a threefold greater percent reduction in fat mass, compared with lean mass, resulting in an overall improvement in body composition,” reported SURMOUNT-1 co-investigator Louis Aronne, MD, Comprehensive Weight Control Center, Weill Cornell Medicine, New York.

Weight loss and body composition explored

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that works to activate the GIP and GLP-1 receptors, respectively, found in areas of the brain important for appetite regulation, decreasing food intake, and modulating fat utilization. 

The phase 3, double-blind, randomized, controlled trial included data from 2,539 adults with a BMI greater than or equal to 30 kg/m² (class I, II, III obesity) or greater than or equal to 27 kg/m² (overweight) with one or more weight-related complications, excluding diabetes. At baseline, mean body weight was 104.8 kg, mean BMI was 38.0 kg/m², and 94.5% of participants had BMI greater than or equal to 30 kg/m².

Patients were randomized to once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks. The primary objective was to show that tirzepatide was superior to placebo in terms of percentage change in body weight and proportion of participants with body-weight reduction of greater than or equal to 5%. The percentage change from baseline body weight and proportion of participants with body weight reduction greater than or equal to 5% were also assessed across BMI categories of greater than or equal to 27 to less than 30 kg/m², greater than or equal to 30 to less than 35 kg/m² (class 1 obesity), greater than or equal to 35 to less than 40 kg/m² (class 2 obesity), and greater than or equal to 40 kg/m² (class 3 obesity).

In addition, in a retrospective subanalysis, body composition was evaluated in a subpopulation that underwent dual-energy x-ray absorptiometry, assessing change from baseline body composition within age subgroups less than 50 years (n = 99), 50-64.9 years (n = 41), and greater than or equal to 65 years (n = 20).

The average weight reduction over the 72 weeks of follow-up was –16.0%, –21.4%, and –22.5% with tirzepatide 5 mg, 10 mg, and 15 mg, compared with –2.4% for participants taking placebo (all P < .001 vs. placebo).

The percentages of participants reaching target weight reductions of greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, greater than or equal to 20%, and greater than or equal to 25% were recorded. Over 90% achieved greater than or equal to 5% weight loss, irrespective of BMI and tirzepatide dose, while 55.5% and 62.9% in the 10-mg and 15-mg groups achieved greater than or equal to 20% weight loss, and 35.0% and 39.7% in the 10-mg and 15-mg groups achieved greater than or equal to 25% weight loss, respectively.

By increasing BMI category, in the 10-mg group, weight loss was –18.2 kg, –21.9 kg, –22.0, and –20.7 kg; and in the 15-mg group, weight loss was –18.1kg, –21.2 kg, –24.5 kg, and –22.8 kg. Weight loss in the 5-mg group ranged from –16.6 kg to –15.9 kg from lowest to highest BMI category. 

“In the lower-weight categories, there is less weight to lose, so we see a flattening of the curve [with a] maximum of around 18%, so it may be that as we learn more about a drug that is so potent, we recognize that we don’t need to use such a high dose in people with BMI 27-30 kg/m²,” he explained. “It’s the higher BMI categories where we need the higher dose.”

As with lifestyle and surgical treatments, participants taking tirzepatide had around a three times greater percentage reduction in fat mass than lean mass, resulting in an overall improvement in body composition, reported Dr. Aronne.

“We want loss of fat, not lean mass, and we know that we lose around one part lean to three parts fat mass when on a diet and exercise regimen,” he went on to explain. “We see exactly this [balance of lean-to-fat-mass loss] here with 33.9% total fat mass reduction in the treatment group, compared with 8.2% in the placebo group.”

Visceral fat mass reduction was 40% in the treatment group, compared with 7.3% with placebo. “It’s good to see there’s more loss of visceral fat,” said Dr. Aronne. Lean mass loss was 10.9%. “So around three times greater reduction in fat over lean mass loss, resulting in overall improvement of body composition,” he reported. 

Also, in older people (≥ 65 years) there was approximately no difference in fat versus lean mass loss, compared with younger people, despite older people being more likely to lose more lean mass.

With respect to patient-reported outcomes based on the 36-item Short-Form Health Survey (SF-36), Dr. Aronne said that physical functioning scores significantly improved at 72 weeks, compared with placebo, particularly in participants with physical function limitations at baseline.

“In an interesting subanalysis, those with physical limitations at baseline showed a significant improvement versus placebo of over 5% difference [considered significant],” he added.

Safety and tolerability were previously reported in the NEJM article. The most common adverse events with tirzepatide were gastrointestinal, and adverse events causing treatment discontinuation occurred in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg doses or placebo, respectively.

“A revolution is coming in the treatment of obesity and cardiometabolic disease, and most physicians cannot grasp this. We’re finally getting the efficacy we’ve been looking for that will produce benefits in every realm,” concluded Dr. Aronne. “These data show that we are now hitting all the secondary endpoints and making our patients better.”

“I think this bodes well. I always envisioned a time when the treatment of obesity would come first before the treatment of cardiometabolic complications of obesity, and I think we’re on the verge of that era with semaglutide, tirzepatide, and the very exciting treatments to come.”

The SURMOUNT-1 trial was sponsored by Lilly. Dr. Aronne is cofounder, chief scientific advisor, and a member of the board of directors for Intellihealth. He is also a paid scientific advisory board member for Eli Lilly.

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

DUBLIN – Ear acupuncture with stimulation beads leads to weight loss and a reduction in both waist circumference and body fat percentage, when combined with restricted food intake, in men with high levels of visceral fat and overweight/obesity.

Edward Olive/Dreamstime.com

Three months of auricular acupuncture stimulation and dietary restriction led to a mean weight loss of nearly 9 kg plus a drop in waist circumference of more than 10 cm.

According to the researchers, acupuncture beads, used in Japan to augment weight loss for more than 30 years, are thought to stimulate nerves and organs that regulate appetite, satiety, hunger, and food cravings.

Findings of the observational study were presented by Takahiro Fujimoto, MD, PhD, Clinic F, Tokyo, at this year’s European Congress on Obesity.

Together with a prior study using the same intervention in women, Dr. Fujimoto and colleagues have now gathered data in more than 1,000 individuals, he said. “We wanted a method that was simple and noninvasive that would serve as a support to exercise and dietary therapy,” Dr. Fujimoto said in an interview.

“We believe there is an effect,” he asserted. “Acupuncture’s effect lies in stimulating the satiety center with benefits in helping individuals to control their food cravings and intake when reducing meals,” he said, pointing out that similar techniques have been used in patients undergoing withdrawal from drug addiction and in smoking cessation. He explained that acupuncture beads are believed to help individuals change their lifestyle habits, and added that “the relapse rate after 6 months is addressed in another paper, and it is very low.”

Professor Jason C.G. Halford, PhD, head of school at the University of Leeds, England, and president of the European Association for the Study of Obesity, commented on the findings. “There is no control group here receiving everything but the acupuncture,” he noted. “As such, it could be other elements of the intervention driving this [effect] including the act of keeping a food diary increasing awareness of one’s diet. A randomized controlled trial would be the next step.”

In women, the technique led to significantly more weight loss than in those who were untreated, and weight loss was maintained for 6 months after the end of treatment.

The researchers added that acupuncture stimulation with beads was a simpler method than traditional use of intradermal needles requiring expert acupuncturists. The stimulation is applied with 1.5-mm metal ear beads on 6 points of the outer ear (shen men, food pipe, upper stomach opening, stomach, lungs, and endocrine system) that correspond to meridian lines, and as such, restores the flow of qi by resolving any blockages or disruption. This may help with a variety of health conditions, according to the researchers. Placed on both ears, surgical tape was used to keep the beads in place to ensure participants continuously received uniform pressure on each of the six acupuncture points.

Dietary guidance was provided to participants to help reduce food intake by half, and nutritional supplements were given to compensate for any deficiencies. Participants attended twice-weekly clinic visits for bead sticking and diet progress monitoring. Body weight, body fat percentage, fat mass, lean mass, muscle mass, body mass index (BMI), and abdominal fat were assessed at the start and end of the study period.

“Since these tiny metal beads are attached to six points on the outer ear that stimulate nerves and organs which regulate appetite, satiety, and hunger, this type of acupuncture does not require complex knowledge or skill,” explained Dr. Fujimoto.

The results of the latest study, in men only, build on a prior study of more than 1,300 women who also received auricular acupuncture stimulation with beads as well as a halving of their food intake. In women, the weight loss program led to total body weight loss of 11.2% over 3 months.

At baseline, the 81 male participants, ages 21-78 years, had a mean BMI of 28.4 kg/m² and mean waist circumference of 98.4 cm. Body fat percentage was 28.2%.

After 3 months, participants lost a mean of 8.6 kg (P < .001), decreased waist circumference by a mean of 10.4 cm (P < .001), and lost a mean of 4.0% of total body fat (P < .001). Visceral fat levels also fell by 2.2 points (P < .001), from 15.2 points at baseline to 13.0 points after 3 months. (A healthy visceral fat rating is between 1 and 12 points.) BMI decreased by almost 3 kg/m² (from 28.4 at baseline to 25.5 at 3 months; P < .001).

Improvement in muscle-to-fat ratio was greater in men than women, whereas women had a greater decrease in percentage body fat than men.

“Whilst receiving ear acupuncture, the investigators asked participants to cut their food intake by half. It’s not unreasonable to expect that this major dietary change was the main reason participants lost weight,” remarked Graham Wheeler, PhD, statistical ambassador at the Royal Statistical Society, United Kingdom.

He also commented on the lack of a control group: “This study does not show us the impact of ear acupuncture on weight loss.”

Dr. Fujimoto and Dr. Halford have reported no relevant financial relationships. Dr. Wheeler is a statistical ambassador for the Royal Statistical Society, is employed by GSK, and holds an honorary senior lecturer post at Imperial College London.

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

DUBLIN – Ear acupuncture with stimulation beads leads to weight loss and a reduction in both waist circumference and body fat percentage, when combined with restricted food intake, in men with high levels of visceral fat and overweight/obesity.

Edward Olive/Dreamstime.com

Three months of auricular acupuncture stimulation and dietary restriction led to a mean weight loss of nearly 9 kg plus a drop in waist circumference of more than 10 cm.

According to the researchers, acupuncture beads, used in Japan to augment weight loss for more than 30 years, are thought to stimulate nerves and organs that regulate appetite, satiety, hunger, and food cravings.

Findings of the observational study were presented by Takahiro Fujimoto, MD, PhD, Clinic F, Tokyo, at this year’s European Congress on Obesity.

Together with a prior study using the same intervention in women, Dr. Fujimoto and colleagues have now gathered data in more than 1,000 individuals, he said. “We wanted a method that was simple and noninvasive that would serve as a support to exercise and dietary therapy,” Dr. Fujimoto said in an interview.

“We believe there is an effect,” he asserted. “Acupuncture’s effect lies in stimulating the satiety center with benefits in helping individuals to control their food cravings and intake when reducing meals,” he said, pointing out that similar techniques have been used in patients undergoing withdrawal from drug addiction and in smoking cessation. He explained that acupuncture beads are believed to help individuals change their lifestyle habits, and added that “the relapse rate after 6 months is addressed in another paper, and it is very low.”

Professor Jason C.G. Halford, PhD, head of school at the University of Leeds, England, and president of the European Association for the Study of Obesity, commented on the findings. “There is no control group here receiving everything but the acupuncture,” he noted. “As such, it could be other elements of the intervention driving this [effect] including the act of keeping a food diary increasing awareness of one’s diet. A randomized controlled trial would be the next step.”

In women, the technique led to significantly more weight loss than in those who were untreated, and weight loss was maintained for 6 months after the end of treatment.

The researchers added that acupuncture stimulation with beads was a simpler method than traditional use of intradermal needles requiring expert acupuncturists. The stimulation is applied with 1.5-mm metal ear beads on 6 points of the outer ear (shen men, food pipe, upper stomach opening, stomach, lungs, and endocrine system) that correspond to meridian lines, and as such, restores the flow of qi by resolving any blockages or disruption. This may help with a variety of health conditions, according to the researchers. Placed on both ears, surgical tape was used to keep the beads in place to ensure participants continuously received uniform pressure on each of the six acupuncture points.

Dietary guidance was provided to participants to help reduce food intake by half, and nutritional supplements were given to compensate for any deficiencies. Participants attended twice-weekly clinic visits for bead sticking and diet progress monitoring. Body weight, body fat percentage, fat mass, lean mass, muscle mass, body mass index (BMI), and abdominal fat were assessed at the start and end of the study period.

“Since these tiny metal beads are attached to six points on the outer ear that stimulate nerves and organs which regulate appetite, satiety, and hunger, this type of acupuncture does not require complex knowledge or skill,” explained Dr. Fujimoto.

The results of the latest study, in men only, build on a prior study of more than 1,300 women who also received auricular acupuncture stimulation with beads as well as a halving of their food intake. In women, the weight loss program led to total body weight loss of 11.2% over 3 months.

At baseline, the 81 male participants, ages 21-78 years, had a mean BMI of 28.4 kg/m² and mean waist circumference of 98.4 cm. Body fat percentage was 28.2%.

After 3 months, participants lost a mean of 8.6 kg (P < .001), decreased waist circumference by a mean of 10.4 cm (P < .001), and lost a mean of 4.0% of total body fat (P < .001). Visceral fat levels also fell by 2.2 points (P < .001), from 15.2 points at baseline to 13.0 points after 3 months. (A healthy visceral fat rating is between 1 and 12 points.) BMI decreased by almost 3 kg/m² (from 28.4 at baseline to 25.5 at 3 months; P < .001).

Improvement in muscle-to-fat ratio was greater in men than women, whereas women had a greater decrease in percentage body fat than men.

“Whilst receiving ear acupuncture, the investigators asked participants to cut their food intake by half. It’s not unreasonable to expect that this major dietary change was the main reason participants lost weight,” remarked Graham Wheeler, PhD, statistical ambassador at the Royal Statistical Society, United Kingdom.

He also commented on the lack of a control group: “This study does not show us the impact of ear acupuncture on weight loss.”

Dr. Fujimoto and Dr. Halford have reported no relevant financial relationships. Dr. Wheeler is a statistical ambassador for the Royal Statistical Society, is employed by GSK, and holds an honorary senior lecturer post at Imperial College London.

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

DUBLIN – Ear acupuncture with stimulation beads leads to weight loss and a reduction in both waist circumference and body fat percentage, when combined with restricted food intake, in men with high levels of visceral fat and overweight/obesity.

Edward Olive/Dreamstime.com

Three months of auricular acupuncture stimulation and dietary restriction led to a mean weight loss of nearly 9 kg plus a drop in waist circumference of more than 10 cm.

According to the researchers, acupuncture beads, used in Japan to augment weight loss for more than 30 years, are thought to stimulate nerves and organs that regulate appetite, satiety, hunger, and food cravings.

Findings of the observational study were presented by Takahiro Fujimoto, MD, PhD, Clinic F, Tokyo, at this year’s European Congress on Obesity.

Together with a prior study using the same intervention in women, Dr. Fujimoto and colleagues have now gathered data in more than 1,000 individuals, he said. “We wanted a method that was simple and noninvasive that would serve as a support to exercise and dietary therapy,” Dr. Fujimoto said in an interview.

“We believe there is an effect,” he asserted. “Acupuncture’s effect lies in stimulating the satiety center with benefits in helping individuals to control their food cravings and intake when reducing meals,” he said, pointing out that similar techniques have been used in patients undergoing withdrawal from drug addiction and in smoking cessation. He explained that acupuncture beads are believed to help individuals change their lifestyle habits, and added that “the relapse rate after 6 months is addressed in another paper, and it is very low.”

Professor Jason C.G. Halford, PhD, head of school at the University of Leeds, England, and president of the European Association for the Study of Obesity, commented on the findings. “There is no control group here receiving everything but the acupuncture,” he noted. “As such, it could be other elements of the intervention driving this [effect] including the act of keeping a food diary increasing awareness of one’s diet. A randomized controlled trial would be the next step.”

In women, the technique led to significantly more weight loss than in those who were untreated, and weight loss was maintained for 6 months after the end of treatment.

The researchers added that acupuncture stimulation with beads was a simpler method than traditional use of intradermal needles requiring expert acupuncturists. The stimulation is applied with 1.5-mm metal ear beads on 6 points of the outer ear (shen men, food pipe, upper stomach opening, stomach, lungs, and endocrine system) that correspond to meridian lines, and as such, restores the flow of qi by resolving any blockages or disruption. This may help with a variety of health conditions, according to the researchers. Placed on both ears, surgical tape was used to keep the beads in place to ensure participants continuously received uniform pressure on each of the six acupuncture points.

Dietary guidance was provided to participants to help reduce food intake by half, and nutritional supplements were given to compensate for any deficiencies. Participants attended twice-weekly clinic visits for bead sticking and diet progress monitoring. Body weight, body fat percentage, fat mass, lean mass, muscle mass, body mass index (BMI), and abdominal fat were assessed at the start and end of the study period.

“Since these tiny metal beads are attached to six points on the outer ear that stimulate nerves and organs which regulate appetite, satiety, and hunger, this type of acupuncture does not require complex knowledge or skill,” explained Dr. Fujimoto.

The results of the latest study, in men only, build on a prior study of more than 1,300 women who also received auricular acupuncture stimulation with beads as well as a halving of their food intake. In women, the weight loss program led to total body weight loss of 11.2% over 3 months.

At baseline, the 81 male participants, ages 21-78 years, had a mean BMI of 28.4 kg/m² and mean waist circumference of 98.4 cm. Body fat percentage was 28.2%.

After 3 months, participants lost a mean of 8.6 kg (P < .001), decreased waist circumference by a mean of 10.4 cm (P < .001), and lost a mean of 4.0% of total body fat (P < .001). Visceral fat levels also fell by 2.2 points (P < .001), from 15.2 points at baseline to 13.0 points after 3 months. (A healthy visceral fat rating is between 1 and 12 points.) BMI decreased by almost 3 kg/m² (from 28.4 at baseline to 25.5 at 3 months; P < .001).

Improvement in muscle-to-fat ratio was greater in men than women, whereas women had a greater decrease in percentage body fat than men.

“Whilst receiving ear acupuncture, the investigators asked participants to cut their food intake by half. It’s not unreasonable to expect that this major dietary change was the main reason participants lost weight,” remarked Graham Wheeler, PhD, statistical ambassador at the Royal Statistical Society, United Kingdom.

He also commented on the lack of a control group: “This study does not show us the impact of ear acupuncture on weight loss.”

Dr. Fujimoto and Dr. Halford have reported no relevant financial relationships. Dr. Wheeler is a statistical ambassador for the Royal Statistical Society, is employed by GSK, and holds an honorary senior lecturer post at Imperial College London.

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

SEOUL, SOUTH KOREA – A panel of urinary biomarkers may do better than measuring proteinuria in predicting which patients with lupus nephritis are going to respond to treatment, according to a presentation at an international congress on systemic lupus erythematosus.

Physician-scientist Andrea Fava, MD, of the division of rheumatology at Johns Hopkins University, Baltimore, presented data from a study using urine proteomics to identify biomarkers present in the urine of patients with lupus nephritis at 3 months after starting treatment that were linked to better outcomes from that treatment at 1 year.

While proteinuria is the standard measure used to guide decisions about whether to do a kidney biopsy and how to treat lupus nephritis, it doesn’t always correlate with what’s actually going on inside the kidney in terms of histology and inflammation, Dr. Fava said.

Bianca Nogrady/MDedge News

He pointed to an earlier study in which researchers did kidney biopsies 6 months after patients with lupus nephritis started treatment with mycophenolate. This suggested that around half of patients who showed a clinical response to treatment – defined as proteinuria below 500 mg/day – still had significant histologic disease activity. Another study suggested that this elevated histologic disease activity is associated with a risk of flare, which can result in significant nephron loss. On the flip side, nearly two-thirds of patients in complete histologic remission still had elevated proteinuria.

Unfortunately, it’s not possible or practical to biopsy patients on a regular basis, Dr. Fava said. “So we need better biomarkers, and to do so, we need better knowledge of the pathophysiology because if we have biomarkers that reflect tissue biology in real-time, that may surely guide personalized treatments,” he said at the congress.

Dr. Fava and colleagues enrolled 225 patients with SLE who were undergoing kidney biopsy and 10 healthy controls and used proteomics to quantify the urinary levels of around 1,200 proteins at baseline, 3, 6, and 12 months after initiating treatment.

The team then analyzed these data to look for protein signatures that correlated with histologic phenotypes – particularly the amount of inflammation in the kidney – and clinical features such as response to treatment.

They found several protein biomarkers that appeared to be linked to histologic activity in the kidney, including interleukin (IL)-16, CD163, and neutrophil granule proteins.

Initially, the team looked at baseline levels of these proteins to see if they predicted who responded to treatment, but found no difference between responders and nonresponders.

However, when they looked at levels at 3 months after treatment, a pattern emerged. “We found that in patients who were not responding, there were no changes after 3 months of treatment in the urine proteome,” Dr. Fava said. Among those who did respond to treatment, the levels of these proteins – IL-16, CD163, galectin-1, and CD206 – decreased significantly.

“So the proteins that are linked to renal activity decrease only in responders, suggesting that effective immunosuppression is effective in reducing intrarenal inflammation, which eventually results in low proteinuria at 1 year.”

The decline in these biomarkers persisted at 1 year, and the study suggested it was a better predictor of which patients would respond to treatment at 1 year than proteinuria.

Dr. Fava said in an interview that better biomarkers could revolutionize the treatment and management of lupus nephritis.

“First of all, it can shift the management strategy from treatment to prevention, because at the very beginning we can nip it in the bud maybe with very gentle treatment,” he said. Different panels of urine biomarkers could identify patients at risk of treatment failure, and also help patients to taper off their immunosuppressive therapy without an increased risk of flare. “If we have a way to tell us there’s still inflammation that needs treatment, that could change the way we do it,” he said.

He acknowledged there are significant challenges to developing these biomarkers for clinical use; one is the decision of how to define disease activity without relying on proteinuria as a measure. “Why do I want a biomarker that can predict another biomarker?” he said.

Another presentation during the same session, by Huihua Ding, MD, of Shanghai Jiao Tong University in Shanghai, China, reported on the use of urinary L-selectin to assess renal disease activity and response to treatment in a multiethnic cohort.

This study, involving 474 patients with SLE with or without renal involvement in the United States and China, found levels of urinary L-selectin were elevated only in patients with active lupus nephritis and showed patterns that correlated with renal histologic characteristics.

Clinical rheumatologist Eric F. Morand, MD, PhD, and head of the School of Clinical Sciences at Monash University in Melbourne said one challenge with using urinary biomarkers was that it was not yet clear what these biomarkers reveal about the kidney. “It will be important to see whether this proteomic data actually link to renal outcomes,” Dr. Morand said in an interview. “I think predicting the response to treatment should be based around GFR [glomerular filtration rate] preservation, and I don’t think I’ve seen data yet that the urine biomarkers are going to tell us how to do that better.”

Dr. Morand is optimistic that urine biomarkers will one day be able to achieve that, but he stressed the importance of having urine biomarker tests available in the field at low cost. “You’re going to be doing the tests repeatedly, so therefore, you’re probably going to need to come down to a smaller list of proteins that you measure.”

Dr. Fava reported receiving support from Sanofi and Annexion Bio.

SEOUL, SOUTH KOREA – A panel of urinary biomarkers may do better than measuring proteinuria in predicting which patients with lupus nephritis are going to respond to treatment, according to a presentation at an international congress on systemic lupus erythematosus.

Physician-scientist Andrea Fava, MD, of the division of rheumatology at Johns Hopkins University, Baltimore, presented data from a study using urine proteomics to identify biomarkers present in the urine of patients with lupus nephritis at 3 months after starting treatment that were linked to better outcomes from that treatment at 1 year.

While proteinuria is the standard measure used to guide decisions about whether to do a kidney biopsy and how to treat lupus nephritis, it doesn’t always correlate with what’s actually going on inside the kidney in terms of histology and inflammation, Dr. Fava said.

Bianca Nogrady/MDedge News

He pointed to an earlier study in which researchers did kidney biopsies 6 months after patients with lupus nephritis started treatment with mycophenolate. This suggested that around half of patients who showed a clinical response to treatment – defined as proteinuria below 500 mg/day – still had significant histologic disease activity. Another study suggested that this elevated histologic disease activity is associated with a risk of flare, which can result in significant nephron loss. On the flip side, nearly two-thirds of patients in complete histologic remission still had elevated proteinuria.

Unfortunately, it’s not possible or practical to biopsy patients on a regular basis, Dr. Fava said. “So we need better biomarkers, and to do so, we need better knowledge of the pathophysiology because if we have biomarkers that reflect tissue biology in real-time, that may surely guide personalized treatments,” he said at the congress.

Dr. Fava and colleagues enrolled 225 patients with SLE who were undergoing kidney biopsy and 10 healthy controls and used proteomics to quantify the urinary levels of around 1,200 proteins at baseline, 3, 6, and 12 months after initiating treatment.

The team then analyzed these data to look for protein signatures that correlated with histologic phenotypes – particularly the amount of inflammation in the kidney – and clinical features such as response to treatment.

They found several protein biomarkers that appeared to be linked to histologic activity in the kidney, including interleukin (IL)-16, CD163, and neutrophil granule proteins.

Initially, the team looked at baseline levels of these proteins to see if they predicted who responded to treatment, but found no difference between responders and nonresponders.

However, when they looked at levels at 3 months after treatment, a pattern emerged. “We found that in patients who were not responding, there were no changes after 3 months of treatment in the urine proteome,” Dr. Fava said. Among those who did respond to treatment, the levels of these proteins – IL-16, CD163, galectin-1, and CD206 – decreased significantly.

“So the proteins that are linked to renal activity decrease only in responders, suggesting that effective immunosuppression is effective in reducing intrarenal inflammation, which eventually results in low proteinuria at 1 year.”

The decline in these biomarkers persisted at 1 year, and the study suggested it was a better predictor of which patients would respond to treatment at 1 year than proteinuria.

Dr. Fava said in an interview that better biomarkers could revolutionize the treatment and management of lupus nephritis.

“First of all, it can shift the management strategy from treatment to prevention, because at the very beginning we can nip it in the bud maybe with very gentle treatment,” he said. Different panels of urine biomarkers could identify patients at risk of treatment failure, and also help patients to taper off their immunosuppressive therapy without an increased risk of flare. “If we have a way to tell us there’s still inflammation that needs treatment, that could change the way we do it,” he said.

He acknowledged there are significant challenges to developing these biomarkers for clinical use; one is the decision of how to define disease activity without relying on proteinuria as a measure. “Why do I want a biomarker that can predict another biomarker?” he said.

Another presentation during the same session, by Huihua Ding, MD, of Shanghai Jiao Tong University in Shanghai, China, reported on the use of urinary L-selectin to assess renal disease activity and response to treatment in a multiethnic cohort.

This study, involving 474 patients with SLE with or without renal involvement in the United States and China, found levels of urinary L-selectin were elevated only in patients with active lupus nephritis and showed patterns that correlated with renal histologic characteristics.

Clinical rheumatologist Eric F. Morand, MD, PhD, and head of the School of Clinical Sciences at Monash University in Melbourne said one challenge with using urinary biomarkers was that it was not yet clear what these biomarkers reveal about the kidney. “It will be important to see whether this proteomic data actually link to renal outcomes,” Dr. Morand said in an interview. “I think predicting the response to treatment should be based around GFR [glomerular filtration rate] preservation, and I don’t think I’ve seen data yet that the urine biomarkers are going to tell us how to do that better.”

Dr. Morand is optimistic that urine biomarkers will one day be able to achieve that, but he stressed the importance of having urine biomarker tests available in the field at low cost. “You’re going to be doing the tests repeatedly, so therefore, you’re probably going to need to come down to a smaller list of proteins that you measure.”

Dr. Fava reported receiving support from Sanofi and Annexion Bio.

SEOUL, SOUTH KOREA – A panel of urinary biomarkers may do better than measuring proteinuria in predicting which patients with lupus nephritis are going to respond to treatment, according to a presentation at an international congress on systemic lupus erythematosus.

Physician-scientist Andrea Fava, MD, of the division of rheumatology at Johns Hopkins University, Baltimore, presented data from a study using urine proteomics to identify biomarkers present in the urine of patients with lupus nephritis at 3 months after starting treatment that were linked to better outcomes from that treatment at 1 year.

While proteinuria is the standard measure used to guide decisions about whether to do a kidney biopsy and how to treat lupus nephritis, it doesn’t always correlate with what’s actually going on inside the kidney in terms of histology and inflammation, Dr. Fava said.

Bianca Nogrady/MDedge News

He pointed to an earlier study in which researchers did kidney biopsies 6 months after patients with lupus nephritis started treatment with mycophenolate. This suggested that around half of patients who showed a clinical response to treatment – defined as proteinuria below 500 mg/day – still had significant histologic disease activity. Another study suggested that this elevated histologic disease activity is associated with a risk of flare, which can result in significant nephron loss. On the flip side, nearly two-thirds of patients in complete histologic remission still had elevated proteinuria.

Unfortunately, it’s not possible or practical to biopsy patients on a regular basis, Dr. Fava said. “So we need better biomarkers, and to do so, we need better knowledge of the pathophysiology because if we have biomarkers that reflect tissue biology in real-time, that may surely guide personalized treatments,” he said at the congress.

Dr. Fava and colleagues enrolled 225 patients with SLE who were undergoing kidney biopsy and 10 healthy controls and used proteomics to quantify the urinary levels of around 1,200 proteins at baseline, 3, 6, and 12 months after initiating treatment.

The team then analyzed these data to look for protein signatures that correlated with histologic phenotypes – particularly the amount of inflammation in the kidney – and clinical features such as response to treatment.

They found several protein biomarkers that appeared to be linked to histologic activity in the kidney, including interleukin (IL)-16, CD163, and neutrophil granule proteins.

Initially, the team looked at baseline levels of these proteins to see if they predicted who responded to treatment, but found no difference between responders and nonresponders.

However, when they looked at levels at 3 months after treatment, a pattern emerged. “We found that in patients who were not responding, there were no changes after 3 months of treatment in the urine proteome,” Dr. Fava said. Among those who did respond to treatment, the levels of these proteins – IL-16, CD163, galectin-1, and CD206 – decreased significantly.

“So the proteins that are linked to renal activity decrease only in responders, suggesting that effective immunosuppression is effective in reducing intrarenal inflammation, which eventually results in low proteinuria at 1 year.”

The decline in these biomarkers persisted at 1 year, and the study suggested it was a better predictor of which patients would respond to treatment at 1 year than proteinuria.

Dr. Fava said in an interview that better biomarkers could revolutionize the treatment and management of lupus nephritis.

“First of all, it can shift the management strategy from treatment to prevention, because at the very beginning we can nip it in the bud maybe with very gentle treatment,” he said. Different panels of urine biomarkers could identify patients at risk of treatment failure, and also help patients to taper off their immunosuppressive therapy without an increased risk of flare. “If we have a way to tell us there’s still inflammation that needs treatment, that could change the way we do it,” he said.

He acknowledged there are significant challenges to developing these biomarkers for clinical use; one is the decision of how to define disease activity without relying on proteinuria as a measure. “Why do I want a biomarker that can predict another biomarker?” he said.

Another presentation during the same session, by Huihua Ding, MD, of Shanghai Jiao Tong University in Shanghai, China, reported on the use of urinary L-selectin to assess renal disease activity and response to treatment in a multiethnic cohort.

This study, involving 474 patients with SLE with or without renal involvement in the United States and China, found levels of urinary L-selectin were elevated only in patients with active lupus nephritis and showed patterns that correlated with renal histologic characteristics.

Clinical rheumatologist Eric F. Morand, MD, PhD, and head of the School of Clinical Sciences at Monash University in Melbourne said one challenge with using urinary biomarkers was that it was not yet clear what these biomarkers reveal about the kidney. “It will be important to see whether this proteomic data actually link to renal outcomes,” Dr. Morand said in an interview. “I think predicting the response to treatment should be based around GFR [glomerular filtration rate] preservation, and I don’t think I’ve seen data yet that the urine biomarkers are going to tell us how to do that better.”

Dr. Morand is optimistic that urine biomarkers will one day be able to achieve that, but he stressed the importance of having urine biomarker tests available in the field at low cost. “You’re going to be doing the tests repeatedly, so therefore, you’re probably going to need to come down to a smaller list of proteins that you measure.”

Dr. Fava reported receiving support from Sanofi and Annexion Bio.