News

TOPLINE:

A new telephone-based program implemented in a Federally Qualified Health Center (FQHC) demonstrates effectiveness in reducing unhealthy alcohol use among diverse adult patients screened using the Alcohol Use Disorders Identification Test (AUDIT).

METHODOLOGY:

• Researchers implemented a screening and team-based telephonic program within a large FQHC system in Texas in which adult patients were routinely screened using AUDIT-Consumption (AUDIT-C) questions.
• The team-based, telecare-centered program was designed to follow-up positive screening results with full AUDIT assessments and to provide a two-session brief intervention for all patients. Patients with AUDIT scores ≥ 12 received the brief intervention along with a referral for additional support or an assessment for pharmacotherapy prescription.
• The researchers screened 3959 patients between March 2021 and May 2023, of whom 412 patients with positive results were successfully contacted and had their AUDIT completed (mean age, 46 years; 32% women; 86% Hispanic/Latino; 65% preferred Spanish).
• Of these, 29 patients had full AUDIT scores ranging from 0 to 3, 252 had scores between 4 and 12, and 131 had scores > 12.
• Follow-up AUDIT assessments conducted at 3-6 months were completed for 251 patients (26% women; 90% Hispanic/Latino), and those with AUDIT scores ≥ 12 were offered additional treatment options, including telecare services, in-person appointments with the addiction medicine clinic, and/or pharmacotherapy.

TAKEAWAY:

• Among the patients with an initial AUDIT score > 12, 19 received pharmacotherapy and 13 had at least one appointment with the addiction medicine service.
• For patients who completed the initial and final follow-ups, the mean change in AUDIT score was −4.1 (95% CI, −3.4 to −4.7).
• Spanish-speaking patients demonstrated a greater reduction in AUDIT scores than English-speaking patients.
• The mean reduction in the AUDIT score at the 3- to 6-month follow-up was larger in those with initial AUDIT scores > 12 than in those with initial AUDIT scores ≤ 12 (7.99 vs 2.25).

IN PRACTICE:

“Our intervention was delivered outside of traditional office visits and did not disrupt clinic flow or add burden to the practice’s providers, who already face significant challenges in serving this high-needs population,” the authors wrote. “We believe this program offers a template for delivering evidence-based, equitable preventive care for unhealthy alcohol use in a diverse patient population.”

SOURCE:

The study was led by Michael Pignone, MD, MPH, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. It was published online in the Journal of General Internal Medicine.

LIMITATIONS:

The lack of systematic tracking for the unsuccessful attempts at establishing contact limited the understanding of the variations in screening positivity and the subsequent engagement in the program. Program staffing and constraints in the budget limited the ability to reach all potentially interested participants. The absence of a control group made it difficult to attribute the observed reductions in the AUDIT scores solely to the intervention. The data on follow-up were collected from only 61% participants, raising the possibility that those who were not reached may have had different outcomes than those who were successfully contacted.

DISCLOSURES:

The Cancer Prevention and Research Institute of Texas provided funding for this program. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new telephone-based program implemented in a Federally Qualified Health Center (FQHC) demonstrates effectiveness in reducing unhealthy alcohol use among diverse adult patients screened using the Alcohol Use Disorders Identification Test (AUDIT).

METHODOLOGY:

• Researchers implemented a screening and team-based telephonic program within a large FQHC system in Texas in which adult patients were routinely screened using AUDIT-Consumption (AUDIT-C) questions.
• The team-based, telecare-centered program was designed to follow-up positive screening results with full AUDIT assessments and to provide a two-session brief intervention for all patients. Patients with AUDIT scores ≥ 12 received the brief intervention along with a referral for additional support or an assessment for pharmacotherapy prescription.
• The researchers screened 3959 patients between March 2021 and May 2023, of whom 412 patients with positive results were successfully contacted and had their AUDIT completed (mean age, 46 years; 32% women; 86% Hispanic/Latino; 65% preferred Spanish).
• Of these, 29 patients had full AUDIT scores ranging from 0 to 3, 252 had scores between 4 and 12, and 131 had scores > 12.
• Follow-up AUDIT assessments conducted at 3-6 months were completed for 251 patients (26% women; 90% Hispanic/Latino), and those with AUDIT scores ≥ 12 were offered additional treatment options, including telecare services, in-person appointments with the addiction medicine clinic, and/or pharmacotherapy.

TAKEAWAY:

• Among the patients with an initial AUDIT score > 12, 19 received pharmacotherapy and 13 had at least one appointment with the addiction medicine service.
• For patients who completed the initial and final follow-ups, the mean change in AUDIT score was −4.1 (95% CI, −3.4 to −4.7).
• Spanish-speaking patients demonstrated a greater reduction in AUDIT scores than English-speaking patients.
• The mean reduction in the AUDIT score at the 3- to 6-month follow-up was larger in those with initial AUDIT scores > 12 than in those with initial AUDIT scores ≤ 12 (7.99 vs 2.25).

IN PRACTICE:

“Our intervention was delivered outside of traditional office visits and did not disrupt clinic flow or add burden to the practice’s providers, who already face significant challenges in serving this high-needs population,” the authors wrote. “We believe this program offers a template for delivering evidence-based, equitable preventive care for unhealthy alcohol use in a diverse patient population.”

SOURCE:

The study was led by Michael Pignone, MD, MPH, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. It was published online in the Journal of General Internal Medicine.

LIMITATIONS:

The lack of systematic tracking for the unsuccessful attempts at establishing contact limited the understanding of the variations in screening positivity and the subsequent engagement in the program. Program staffing and constraints in the budget limited the ability to reach all potentially interested participants. The absence of a control group made it difficult to attribute the observed reductions in the AUDIT scores solely to the intervention. The data on follow-up were collected from only 61% participants, raising the possibility that those who were not reached may have had different outcomes than those who were successfully contacted.

DISCLOSURES:

The Cancer Prevention and Research Institute of Texas provided funding for this program. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new telephone-based program implemented in a Federally Qualified Health Center (FQHC) demonstrates effectiveness in reducing unhealthy alcohol use among diverse adult patients screened using the Alcohol Use Disorders Identification Test (AUDIT).

METHODOLOGY:

• Researchers implemented a screening and team-based telephonic program within a large FQHC system in Texas in which adult patients were routinely screened using AUDIT-Consumption (AUDIT-C) questions.
• The team-based, telecare-centered program was designed to follow-up positive screening results with full AUDIT assessments and to provide a two-session brief intervention for all patients. Patients with AUDIT scores ≥ 12 received the brief intervention along with a referral for additional support or an assessment for pharmacotherapy prescription.
• The researchers screened 3959 patients between March 2021 and May 2023, of whom 412 patients with positive results were successfully contacted and had their AUDIT completed (mean age, 46 years; 32% women; 86% Hispanic/Latino; 65% preferred Spanish).
• Of these, 29 patients had full AUDIT scores ranging from 0 to 3, 252 had scores between 4 and 12, and 131 had scores > 12.
• Follow-up AUDIT assessments conducted at 3-6 months were completed for 251 patients (26% women; 90% Hispanic/Latino), and those with AUDIT scores ≥ 12 were offered additional treatment options, including telecare services, in-person appointments with the addiction medicine clinic, and/or pharmacotherapy.

TAKEAWAY:

• Among the patients with an initial AUDIT score > 12, 19 received pharmacotherapy and 13 had at least one appointment with the addiction medicine service.
• For patients who completed the initial and final follow-ups, the mean change in AUDIT score was −4.1 (95% CI, −3.4 to −4.7).
• Spanish-speaking patients demonstrated a greater reduction in AUDIT scores than English-speaking patients.
• The mean reduction in the AUDIT score at the 3- to 6-month follow-up was larger in those with initial AUDIT scores > 12 than in those with initial AUDIT scores ≤ 12 (7.99 vs 2.25).

IN PRACTICE:

“Our intervention was delivered outside of traditional office visits and did not disrupt clinic flow or add burden to the practice’s providers, who already face significant challenges in serving this high-needs population,” the authors wrote. “We believe this program offers a template for delivering evidence-based, equitable preventive care for unhealthy alcohol use in a diverse patient population.”

SOURCE:

The study was led by Michael Pignone, MD, MPH, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. It was published online in the Journal of General Internal Medicine.

LIMITATIONS:

The lack of systematic tracking for the unsuccessful attempts at establishing contact limited the understanding of the variations in screening positivity and the subsequent engagement in the program. Program staffing and constraints in the budget limited the ability to reach all potentially interested participants. The absence of a control group made it difficult to attribute the observed reductions in the AUDIT scores solely to the intervention. The data on follow-up were collected from only 61% participants, raising the possibility that those who were not reached may have had different outcomes than those who were successfully contacted.

DISCLOSURES:

The Cancer Prevention and Research Institute of Texas provided funding for this program. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved ustekinumab-stba (Steqeyma) as a biosimilar to the interleukin-12 and -23 inhibitor ustekinumab (Stelara) for the treatment of adults with active Crohn’s disease or ulcerative colitis and for both children aged ≥ 6 years and adults with moderate to severe plaque psoriasis or active psoriatic arthritis.

This is the seventh ustekinumab biosimilar approved by the FDA. The biosimilar, developed by Celltrion, has a license entry date in February 2025 as part of the settlement and license agreement with the manufacturer of the reference biologic, Johnson & Johnson.

Ustekinumab-stba will be available in two formulations: A subcutaneous injection in two strengths — a 45 mg/0.5 mL or 90 mg/1 mL solution in a single-dose, prefilled syringe — and an intravenous infusion of a 130 mg/26 mL (5 mg/mL) solution in a single-dose vial.

“The approval of Steqeyma reflects Celltrion’s continued investment in providing treatment options to patients diagnosed with ulcerative colitis, Crohn’s disease, psoriasis, and psoriatic arthritis,” said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA, Jersey City, New Jersey, in a press release.

The FDA has previously approved the company’s adalimumab biosimilar Yuflyma and its infliximab biosimilar Zymfentra.

The full prescribing information for ustekinumab-stba is available here.

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

The Food and Drug Administration (FDA) has approved ustekinumab-stba (Steqeyma) as a biosimilar to the interleukin-12 and -23 inhibitor ustekinumab (Stelara) for the treatment of adults with active Crohn’s disease or ulcerative colitis and for both children aged ≥ 6 years and adults with moderate to severe plaque psoriasis or active psoriatic arthritis.

This is the seventh ustekinumab biosimilar approved by the FDA. The biosimilar, developed by Celltrion, has a license entry date in February 2025 as part of the settlement and license agreement with the manufacturer of the reference biologic, Johnson & Johnson.

Ustekinumab-stba will be available in two formulations: A subcutaneous injection in two strengths — a 45 mg/0.5 mL or 90 mg/1 mL solution in a single-dose, prefilled syringe — and an intravenous infusion of a 130 mg/26 mL (5 mg/mL) solution in a single-dose vial.

“The approval of Steqeyma reflects Celltrion’s continued investment in providing treatment options to patients diagnosed with ulcerative colitis, Crohn’s disease, psoriasis, and psoriatic arthritis,” said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA, Jersey City, New Jersey, in a press release.

The FDA has previously approved the company’s adalimumab biosimilar Yuflyma and its infliximab biosimilar Zymfentra.

The full prescribing information for ustekinumab-stba is available here.

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

The Food and Drug Administration (FDA) has approved ustekinumab-stba (Steqeyma) as a biosimilar to the interleukin-12 and -23 inhibitor ustekinumab (Stelara) for the treatment of adults with active Crohn’s disease or ulcerative colitis and for both children aged ≥ 6 years and adults with moderate to severe plaque psoriasis or active psoriatic arthritis.

This is the seventh ustekinumab biosimilar approved by the FDA. The biosimilar, developed by Celltrion, has a license entry date in February 2025 as part of the settlement and license agreement with the manufacturer of the reference biologic, Johnson & Johnson.

Ustekinumab-stba will be available in two formulations: A subcutaneous injection in two strengths — a 45 mg/0.5 mL or 90 mg/1 mL solution in a single-dose, prefilled syringe — and an intravenous infusion of a 130 mg/26 mL (5 mg/mL) solution in a single-dose vial.

“The approval of Steqeyma reflects Celltrion’s continued investment in providing treatment options to patients diagnosed with ulcerative colitis, Crohn’s disease, psoriasis, and psoriatic arthritis,” said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA, Jersey City, New Jersey, in a press release.

The FDA has previously approved the company’s adalimumab biosimilar Yuflyma and its infliximab biosimilar Zymfentra.

The full prescribing information for ustekinumab-stba is available here.

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

OVIEDO, SPAIN – In April 2023, the Navarra Pharmacovigilance Center (NPC) became aware of a case involving an infant who developed progressive hair growth on their back, legs, and thighs (hypertrichosis) over the course of 2 months. During an interview with the family, it was revealed that the infant’s father had been using 5% topical minoxidil to treat androgenic alopecia, and he had taken a leave of absence from work to care for his child. After the medication was discontinued, the infant’s symptoms fully regressed. Specialists from the NPC presented the case at the 13th Spanish Pharmacovigilance Congress in November 2024.

A review of similar cases reported in the Spanish Pharmacovigilance System database identified six additional cases with the same characteristics, all involving infants whose caregivers were using minoxidil. Four more cases were found through the European pharmacovigilance database EudraVigilance and a review of scientific literature, bringing the total to 11 cases.

According to the Navarra Pharmacovigilance Bulletin, these cases are concerning as they highlight the exposure of vulnerable infants to a medication not indicated for their age group. Additionally, the condition can cause significant stress for the families of the affected children.

 

Mechanism of Transmission Unclear

The exact mechanism by which caregivers transfer minoxidil to infants is not fully understood. In the newly identified cases, specialists suspect the drug was transmitted through direct or indirect contact. Accidental ingestion is also a possibility if the infant’s hands touched treated areas on the caregiver’s skin and were then brought to the mouth.

The NPC explained that infants’ skin is more permeable because of the thinner stratum corneum and a higher surface area/body weight ratio, making them more susceptible to absorbing topically applied medications.

 

Regulatory Changes and Precautions

In light of these findings, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee concluded that, starting in October 2024, product information for medications containing minoxidil should be updated. Specifically, new information must be added to the package insert warning about the risk for hypertrichosis in infants following accidental exposure to minoxidil.

The NPC emphasizes the importance of caregivers being aware of the risks associated with topical medications like minoxidil. Recommended precautions include thoroughly washing hands after applying the product and covering treated areas to prevent direct contact with infants’ skin.

Healthcare professionals should also be aware of this risk and consider it when diagnosing hypertrichosis in infants. Recognizing the connection can prevent unnecessary testing for the infant and alleviate stress for the family.

This story was translated from Univadis Spain using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

OVIEDO, SPAIN – In April 2023, the Navarra Pharmacovigilance Center (NPC) became aware of a case involving an infant who developed progressive hair growth on their back, legs, and thighs (hypertrichosis) over the course of 2 months. During an interview with the family, it was revealed that the infant’s father had been using 5% topical minoxidil to treat androgenic alopecia, and he had taken a leave of absence from work to care for his child. After the medication was discontinued, the infant’s symptoms fully regressed. Specialists from the NPC presented the case at the 13th Spanish Pharmacovigilance Congress in November 2024.

A review of similar cases reported in the Spanish Pharmacovigilance System database identified six additional cases with the same characteristics, all involving infants whose caregivers were using minoxidil. Four more cases were found through the European pharmacovigilance database EudraVigilance and a review of scientific literature, bringing the total to 11 cases.

According to the Navarra Pharmacovigilance Bulletin, these cases are concerning as they highlight the exposure of vulnerable infants to a medication not indicated for their age group. Additionally, the condition can cause significant stress for the families of the affected children.

 

Mechanism of Transmission Unclear

The exact mechanism by which caregivers transfer minoxidil to infants is not fully understood. In the newly identified cases, specialists suspect the drug was transmitted through direct or indirect contact. Accidental ingestion is also a possibility if the infant’s hands touched treated areas on the caregiver’s skin and were then brought to the mouth.

The NPC explained that infants’ skin is more permeable because of the thinner stratum corneum and a higher surface area/body weight ratio, making them more susceptible to absorbing topically applied medications.

 

Regulatory Changes and Precautions

In light of these findings, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee concluded that, starting in October 2024, product information for medications containing minoxidil should be updated. Specifically, new information must be added to the package insert warning about the risk for hypertrichosis in infants following accidental exposure to minoxidil.

The NPC emphasizes the importance of caregivers being aware of the risks associated with topical medications like minoxidil. Recommended precautions include thoroughly washing hands after applying the product and covering treated areas to prevent direct contact with infants’ skin.

Healthcare professionals should also be aware of this risk and consider it when diagnosing hypertrichosis in infants. Recognizing the connection can prevent unnecessary testing for the infant and alleviate stress for the family.

This story was translated from Univadis Spain using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

OVIEDO, SPAIN – In April 2023, the Navarra Pharmacovigilance Center (NPC) became aware of a case involving an infant who developed progressive hair growth on their back, legs, and thighs (hypertrichosis) over the course of 2 months. During an interview with the family, it was revealed that the infant’s father had been using 5% topical minoxidil to treat androgenic alopecia, and he had taken a leave of absence from work to care for his child. After the medication was discontinued, the infant’s symptoms fully regressed. Specialists from the NPC presented the case at the 13th Spanish Pharmacovigilance Congress in November 2024.

A review of similar cases reported in the Spanish Pharmacovigilance System database identified six additional cases with the same characteristics, all involving infants whose caregivers were using minoxidil. Four more cases were found through the European pharmacovigilance database EudraVigilance and a review of scientific literature, bringing the total to 11 cases.

According to the Navarra Pharmacovigilance Bulletin, these cases are concerning as they highlight the exposure of vulnerable infants to a medication not indicated for their age group. Additionally, the condition can cause significant stress for the families of the affected children.

 

Mechanism of Transmission Unclear

The exact mechanism by which caregivers transfer minoxidil to infants is not fully understood. In the newly identified cases, specialists suspect the drug was transmitted through direct or indirect contact. Accidental ingestion is also a possibility if the infant’s hands touched treated areas on the caregiver’s skin and were then brought to the mouth.

The NPC explained that infants’ skin is more permeable because of the thinner stratum corneum and a higher surface area/body weight ratio, making them more susceptible to absorbing topically applied medications.

 

Regulatory Changes and Precautions

In light of these findings, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee concluded that, starting in October 2024, product information for medications containing minoxidil should be updated. Specifically, new information must be added to the package insert warning about the risk for hypertrichosis in infants following accidental exposure to minoxidil.

The NPC emphasizes the importance of caregivers being aware of the risks associated with topical medications like minoxidil. Recommended precautions include thoroughly washing hands after applying the product and covering treated areas to prevent direct contact with infants’ skin.

Healthcare professionals should also be aware of this risk and consider it when diagnosing hypertrichosis in infants. Recognizing the connection can prevent unnecessary testing for the infant and alleviate stress for the family.

This story was translated from Univadis Spain using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising. 

More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report.¹ However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS.² Among those who had, less than one third (29%) knew how to diagnose the condition. 

Here are 5 things clinicians need to know about AGS.

 

1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.

In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia. 

While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults. 

Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found. 

 

2. Tick bites are only one risk factor for developing AGS. 

Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.³ 

Research has also shown that environmental risk factors could contribute to developing AGS,⁴ like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush. 

Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.

 

3. Symptoms of AGS are consistently inconsistent.

There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.

Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite. 

 

4. Diagnosing AGS requires a combination of a blood test and a physical exam.

Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS. 

Consider the test results along with your patient’s symptoms and risk factors.

 

5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.

People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency–registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities. 

Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.

For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.

Dr. Kersh is Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and disclosed no relevant conflicts of interest.

CDC resources:

About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Resources | Alpha-gal Syndrome | CDC 

References 

Thompson JM et al. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. 

Carpenter A et al. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Taylor ML et al. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759.e2-764.e2. Kersh GJ et al. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478.

Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising. 

More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report.¹ However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS.² Among those who had, less than one third (29%) knew how to diagnose the condition. 

Here are 5 things clinicians need to know about AGS.

 

1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.

In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia. 

While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults. 

Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found. 

 

2. Tick bites are only one risk factor for developing AGS. 

Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.³ 

Research has also shown that environmental risk factors could contribute to developing AGS,⁴ like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush. 

Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.

 

3. Symptoms of AGS are consistently inconsistent.

There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.

Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite. 

 

4. Diagnosing AGS requires a combination of a blood test and a physical exam.

Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS. 

Consider the test results along with your patient’s symptoms and risk factors.

 

5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.

People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency–registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities. 

Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.

For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.

Dr. Kersh is Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and disclosed no relevant conflicts of interest.

CDC resources:

About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Resources | Alpha-gal Syndrome | CDC 

References 

Thompson JM et al. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. 

Carpenter A et al. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Taylor ML et al. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759.e2-764.e2. Kersh GJ et al. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478.

Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising. 

More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report.¹ However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS.² Among those who had, less than one third (29%) knew how to diagnose the condition. 

Here are 5 things clinicians need to know about AGS.

 

1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.

In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia. 

While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults. 

Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found. 

 

2. Tick bites are only one risk factor for developing AGS. 

Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.³ 

Research has also shown that environmental risk factors could contribute to developing AGS,⁴ like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush. 

Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.

 

3. Symptoms of AGS are consistently inconsistent.

There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.

Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite. 

 

4. Diagnosing AGS requires a combination of a blood test and a physical exam.

Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS. 

Consider the test results along with your patient’s symptoms and risk factors.

 

5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.

People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency–registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities. 

Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.

For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.

Dr. Kersh is Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and disclosed no relevant conflicts of interest.

CDC resources:

About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Resources | Alpha-gal Syndrome | CDC 

References 

Thompson JM et al. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. 

Carpenter A et al. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Taylor ML et al. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759.e2-764.e2. Kersh GJ et al. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478.

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Every year, an estimated 45 million Americans attempt some kind of diet to shed weight, especially after the holidays. Whether or not an individual is on a successful weight loss journey, at some point they probably will experience “diet fatigue.” This is the mental and emotional exhaustion associated with engaging in dieting behaviors like calorie counting, weighing and measuring food, meal planning and prepping, and restricting certain foods. 

Diet fatigue is a huge reason (but certainly not the only reason) why diets fail, as dieters can become so burned out that they ditch their diet, return to their former eating habits, blame themselves for their diet failure, and then repeat the cycle.

Alison* became my client just as her diet fatigue was starting to settle in. She had already lost 25 pounds in the prior 6 months while in a coaching program that focused primarily on hitting calorie and macro targets. She had been following an extremely high-protein regimen that relied heavily on animal sources and protein powders. I’m not against using powders to supplement protein needs, but in Alison’s case, she was consuming a powder-and-milk concoction twice per day in place of a meal with actual food. Not only had she become plain sick of the powder, but she was also concerned that all the protein was pushing vegetables off her plate. Alison had been following this plan quite strictly but admitted to indulging in weekend sweets. She recognized that this occasional indulgence could quickly morph into a full-on habit and undo her progress. While Alison had not yet reached her goal weight, we both agreed that she needed to change up her eating routine. 

Getting a patient through diet fatigue involves identifying which dieting behaviors are causing them the most angst and then guiding them toward a more sustainable approach that provides a similar benefit. For example, many dieters develop a huge disdain for calorie tracking, which they most often describe as tedious. One alternative to tracking calories is food journaling, which encourages accountability and mindfulness but is not as time-consuming as plugging every single ingredient you ingest into an app. Alison, however, didn’t have a problem with tracking, nor with weighing her food (as a Type A personality, she preferred having this kind of control). But she was clearly lacking a few things in her previous diet: variety, fiber, and flavor. In short, Alison was not enjoying her food — hence, her increased desire for treats on weekends, which she saw as a kind of reward for “being good” all week. 

To keep Alison from slipping into a weekend bingeing pattern, we discussed a few tweaks to her regimen. First, we had to ditch the protein powder in favor of balanced meals. I recommended reducing her daily protein target, which I felt was unnecessarily high. This provided some wiggle room to add a well-rounded dinner. I encouraged her to start adding spices and herbs to make dishes more exciting. 

Finally — and this one might be controversial — I encouraged Alison to actually plan for a weekly indulgence. In my experience working in the weight management space, complete restriction of a desired food always backfires, so it made sense for Alison to simply build the chocolate into her plan in a reasonable way. 

I’m confident that Alison will reach her weight loss goal (and keep the weight off) if food continues to bring her pleasure. When it comes to weight loss, I believe that if the solution is temporary, success will also be temporary. As a dietitian, preaching sustainable, long-term habit changes is my priority, not just because it’s responsible, but because it’s the only approach that truly works.

*Patient’s name changed to protect privacy. 

Ms. Hanks is a registered dietitian at Well by Messer in New York City. She disclosed no relevant conflicts of interest.

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

Every year, an estimated 45 million Americans attempt some kind of diet to shed weight, especially after the holidays. Whether or not an individual is on a successful weight loss journey, at some point they probably will experience “diet fatigue.” This is the mental and emotional exhaustion associated with engaging in dieting behaviors like calorie counting, weighing and measuring food, meal planning and prepping, and restricting certain foods. 

Diet fatigue is a huge reason (but certainly not the only reason) why diets fail, as dieters can become so burned out that they ditch their diet, return to their former eating habits, blame themselves for their diet failure, and then repeat the cycle.

Alison* became my client just as her diet fatigue was starting to settle in. She had already lost 25 pounds in the prior 6 months while in a coaching program that focused primarily on hitting calorie and macro targets. She had been following an extremely high-protein regimen that relied heavily on animal sources and protein powders. I’m not against using powders to supplement protein needs, but in Alison’s case, she was consuming a powder-and-milk concoction twice per day in place of a meal with actual food. Not only had she become plain sick of the powder, but she was also concerned that all the protein was pushing vegetables off her plate. Alison had been following this plan quite strictly but admitted to indulging in weekend sweets. She recognized that this occasional indulgence could quickly morph into a full-on habit and undo her progress. While Alison had not yet reached her goal weight, we both agreed that she needed to change up her eating routine. 

Getting a patient through diet fatigue involves identifying which dieting behaviors are causing them the most angst and then guiding them toward a more sustainable approach that provides a similar benefit. For example, many dieters develop a huge disdain for calorie tracking, which they most often describe as tedious. One alternative to tracking calories is food journaling, which encourages accountability and mindfulness but is not as time-consuming as plugging every single ingredient you ingest into an app. Alison, however, didn’t have a problem with tracking, nor with weighing her food (as a Type A personality, she preferred having this kind of control). But she was clearly lacking a few things in her previous diet: variety, fiber, and flavor. In short, Alison was not enjoying her food — hence, her increased desire for treats on weekends, which she saw as a kind of reward for “being good” all week. 

To keep Alison from slipping into a weekend bingeing pattern, we discussed a few tweaks to her regimen. First, we had to ditch the protein powder in favor of balanced meals. I recommended reducing her daily protein target, which I felt was unnecessarily high. This provided some wiggle room to add a well-rounded dinner. I encouraged her to start adding spices and herbs to make dishes more exciting. 

Finally — and this one might be controversial — I encouraged Alison to actually plan for a weekly indulgence. In my experience working in the weight management space, complete restriction of a desired food always backfires, so it made sense for Alison to simply build the chocolate into her plan in a reasonable way. 

I’m confident that Alison will reach her weight loss goal (and keep the weight off) if food continues to bring her pleasure. When it comes to weight loss, I believe that if the solution is temporary, success will also be temporary. As a dietitian, preaching sustainable, long-term habit changes is my priority, not just because it’s responsible, but because it’s the only approach that truly works.

*Patient’s name changed to protect privacy. 

Ms. Hanks is a registered dietitian at Well by Messer in New York City. She disclosed no relevant conflicts of interest.

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

Every year, an estimated 45 million Americans attempt some kind of diet to shed weight, especially after the holidays. Whether or not an individual is on a successful weight loss journey, at some point they probably will experience “diet fatigue.” This is the mental and emotional exhaustion associated with engaging in dieting behaviors like calorie counting, weighing and measuring food, meal planning and prepping, and restricting certain foods. 

Diet fatigue is a huge reason (but certainly not the only reason) why diets fail, as dieters can become so burned out that they ditch their diet, return to their former eating habits, blame themselves for their diet failure, and then repeat the cycle.

Alison* became my client just as her diet fatigue was starting to settle in. She had already lost 25 pounds in the prior 6 months while in a coaching program that focused primarily on hitting calorie and macro targets. She had been following an extremely high-protein regimen that relied heavily on animal sources and protein powders. I’m not against using powders to supplement protein needs, but in Alison’s case, she was consuming a powder-and-milk concoction twice per day in place of a meal with actual food. Not only had she become plain sick of the powder, but she was also concerned that all the protein was pushing vegetables off her plate. Alison had been following this plan quite strictly but admitted to indulging in weekend sweets. She recognized that this occasional indulgence could quickly morph into a full-on habit and undo her progress. While Alison had not yet reached her goal weight, we both agreed that she needed to change up her eating routine. 

Getting a patient through diet fatigue involves identifying which dieting behaviors are causing them the most angst and then guiding them toward a more sustainable approach that provides a similar benefit. For example, many dieters develop a huge disdain for calorie tracking, which they most often describe as tedious. One alternative to tracking calories is food journaling, which encourages accountability and mindfulness but is not as time-consuming as plugging every single ingredient you ingest into an app. Alison, however, didn’t have a problem with tracking, nor with weighing her food (as a Type A personality, she preferred having this kind of control). But she was clearly lacking a few things in her previous diet: variety, fiber, and flavor. In short, Alison was not enjoying her food — hence, her increased desire for treats on weekends, which she saw as a kind of reward for “being good” all week. 

To keep Alison from slipping into a weekend bingeing pattern, we discussed a few tweaks to her regimen. First, we had to ditch the protein powder in favor of balanced meals. I recommended reducing her daily protein target, which I felt was unnecessarily high. This provided some wiggle room to add a well-rounded dinner. I encouraged her to start adding spices and herbs to make dishes more exciting. 

Finally — and this one might be controversial — I encouraged Alison to actually plan for a weekly indulgence. In my experience working in the weight management space, complete restriction of a desired food always backfires, so it made sense for Alison to simply build the chocolate into her plan in a reasonable way. 

I’m confident that Alison will reach her weight loss goal (and keep the weight off) if food continues to bring her pleasure. When it comes to weight loss, I believe that if the solution is temporary, success will also be temporary. As a dietitian, preaching sustainable, long-term habit changes is my priority, not just because it’s responsible, but because it’s the only approach that truly works.

*Patient’s name changed to protect privacy. 

Ms. Hanks is a registered dietitian at Well by Messer in New York City. She disclosed no relevant conflicts of interest.

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

Of all the currently available pharmacological and nonpharmacological therapies for attention deficit and hyperactivity disorder (ADHD) in adults, only stimulants and atomoxetine are effective at reducing core symptoms, results of a large comprehensive meta-analysis showed.

The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.

Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.

“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.

The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.

The study was published online in The Lancet Psychiatry. 

 

Bridging the Knowledge Gap

Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.

To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.

For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.

For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.

There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.

In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.

However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.

And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.

Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.

“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”

Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.

 

Experts Weigh In 

Several experts weighed in on the results in a statement from the UK Science Media Center.

Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”

Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”

The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.

“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”

Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.

“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.

In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.

“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.

This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.

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

Of all the currently available pharmacological and nonpharmacological therapies for attention deficit and hyperactivity disorder (ADHD) in adults, only stimulants and atomoxetine are effective at reducing core symptoms, results of a large comprehensive meta-analysis showed.

The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.

Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.

“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.

The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.

The study was published online in The Lancet Psychiatry. 

 

Bridging the Knowledge Gap

Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.

To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.

For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.

For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.

There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.

In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.

However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.

And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.

Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.

“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”

Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.

 

Experts Weigh In 

Several experts weighed in on the results in a statement from the UK Science Media Center.

Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”

Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”

The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.

“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”

Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.

“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.

In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.

“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.

This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.

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

Of all the currently available pharmacological and nonpharmacological therapies for attention deficit and hyperactivity disorder (ADHD) in adults, only stimulants and atomoxetine are effective at reducing core symptoms, results of a large comprehensive meta-analysis showed.

The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.

Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.

“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.

The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.

The study was published online in The Lancet Psychiatry. 

 

Bridging the Knowledge Gap

Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.

To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.

For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.

For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.

There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.

In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.

However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.

And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.

Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.

“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”

Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.

 

Experts Weigh In 

Several experts weighed in on the results in a statement from the UK Science Media Center.

Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”

Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”

The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.

“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”

Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.

“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.

In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.

“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.

This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.

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

NEW YORK, NY — Work over the past several years has reframed hidradenitis suppurativa (HS) as a large-field inflammatory process, a recharacterization that has immediate relevance to treatment strategies and goals, according to two investigators intimately involved in much of the recent progress.

“Success is being achieved by targeting multiple inflammatory axes in HS, and therapeutics are evolving rapidly,” reported James G. Krueger, MD, PhD, head of the Laboratory of Investigative Dermatology, Rockefeller University, New York, NY.

The activity of targeted anti-inflammatory therapies — bimekizumab just joined adalimumab and secukinumab as a third approved biologic for HS — is not news, but the degree to which inflammation is upregulated systemically, not just at areas of skin involvement, has changed the conceptualization of HS.

HS Is a Systemic Inflammatory Disease

Relative to psoriasis, for which there are many parallels, “HS is hugely more inflammatory in the systemic circulation,” Krueger said at the 27th Annual Winter Symposium — Advances in Medical and Surgical Dermatology (MSWS) 2024. Yet, HS is also more complex involving additional pathways that appear to include dysbiosis. The concept of follicular occlusion, once a common explanation for HS, has been left far behind.

“Unlike psoriasis, which we can treat really well by inhibiting a single pathway target, HS is just not that simple,” Krueger said. Although largely an inflammatory process, the cascade of inflammatory factors for specific manifestations, such as tunnels, means that optimal therapy in one case might have little benefit in another.

The relatively new evidence that HS activity is not confined to lesional skin might be the most important recent step toward new strategies to target disease. These studies were performed by Kristina Navrazhina, MD, PhD, now a resident in dermatology at the Icahn School of Medicine at Mount Sinai, New York. She received her PhD while studying HS activity in non-lesional skin. Her work has led her to conclude that the best chance for better outcomes in HS is early diagnosis and treatment. Although this is generally true of any pathology, the changes in the HS phenotype once fistulae form includes a poor response to conventional therapies. 

In fact, based on her work in evaluating HS activity in non-lesional skin, Navrazhina has shown that “many patients with modest lesions already have advanced disease.” Consistent with the premise that HS is a deeply systemic inflammatory process, nodules, considered an early manifestation, turn out to be “the tip of the iceberg.”

 

Non-Lesional HS Skin Is Inflamed

When she has employed RNA sequencing based on tape strip sampling from completely normal skin away from nodules, interleukin (IL)-17 and a broad array of other inflammatory markers were found to be upregulated. When she performed ultrasound to look for disease activity under the normal skin, she has often found tunnels already formed. Doppler ultrasound showed some of these tunnels were actively draining.

This might provide a partial explanation for why therapies are not always effective even when clinical signs of disease are modest. 

“Are we missing the opportunity for intervening?” Navrazhina asked, noting that early intervention has been limited traditionally by extremely long diagnostic delays. Citing the literature, Navrazhina said the average delay is 7 years for HS versus 1 year for psoriasis. Patients often cycle through 3 or 4 providers before the diagnosis is made, she said.

Awakening first-line clinicians to the signs and symptoms of HS, whether in the emergency room or primary care, is a critical message because of the incrementally difficult task to control disease once fistulae have formed. 

Krueger made the same appeal. For the neutrophilic inflammation that characterizes nodules, targeted therapies are often effective, but he agreed that available therapies are generally far less so once tunnels form.

 

Role Seen for Bacteria in HS Pathogenesis

One reason might be an interaction between anaerobic bacteria and the keratinocytes that form the tunnel walls, according to Krueger. Although HS is not typically considered an infectious disease, he reported that the interaction of these bacteria with keratinocytes is associated with expression of approximately 1000 inflammatory gene products. The process of tunnel formation is traced to how factors recruited by upregulated inflammation, such as chemokines, coordinate.

He described recent work pursing novel strategies such as highly targeted antibiotics or inhibitors of complement factor C5a, which has been proposed as a biomarker for HS, to intervene in preventing or reversing HS tunnels. 

While this work progresses, one of the most Important unmet needs in HS is an accepted measure of clinically meaningful improvement in advanced disease, particularly the impact of therapy on HS tunnels, according to Krueger. 

“There is no measure of tunnel activity that the FDA accepts in evaluating drugs,” he noted, which will be essential for approving therapies that offer this benefit. 

A phase 3 trials program for one of the promising drugs, sonelokimab, was announced early in 2024. A nanobody that targets IL-17A/A, IL-17A/F, and IL-17F/F, the small size of this molecule permits exceptional tissue penetration while the broad anti-IL-17 activity has a high degree of theoretical potential in late-stage HS, according to Krueger. 

There are numerous pieces of the HS puzzle that are still missing, but both Krueger and Navrazhina are enthusiastic about new targets and opportunities for disease control that are stemming from a better understanding of the underlying pathophysiology. Not least, both indicated that testing for inflammatory phenotypes will allow for individualized therapeutic choices with a maximum likelihood of response, particularly if earlier diagnosis permits earlier treatment. 

“Due to the heterogeneity of HS, it is hard to know who will respond to which treatment or which treatment should be started first,” Navrazhina said. She thinks that early measures of the inflammatory profile in nodules or even non-lesional skin might provide that guidance. 

Both Krueger and Navrazhina reported no financial relationships relevant to this work. 

 

A version of this article appeared on Medscape.com.

NEW YORK, NY — Work over the past several years has reframed hidradenitis suppurativa (HS) as a large-field inflammatory process, a recharacterization that has immediate relevance to treatment strategies and goals, according to two investigators intimately involved in much of the recent progress.

“Success is being achieved by targeting multiple inflammatory axes in HS, and therapeutics are evolving rapidly,” reported James G. Krueger, MD, PhD, head of the Laboratory of Investigative Dermatology, Rockefeller University, New York, NY.

The activity of targeted anti-inflammatory therapies — bimekizumab just joined adalimumab and secukinumab as a third approved biologic for HS — is not news, but the degree to which inflammation is upregulated systemically, not just at areas of skin involvement, has changed the conceptualization of HS.

HS Is a Systemic Inflammatory Disease

Relative to psoriasis, for which there are many parallels, “HS is hugely more inflammatory in the systemic circulation,” Krueger said at the 27th Annual Winter Symposium — Advances in Medical and Surgical Dermatology (MSWS) 2024. Yet, HS is also more complex involving additional pathways that appear to include dysbiosis. The concept of follicular occlusion, once a common explanation for HS, has been left far behind.

“Unlike psoriasis, which we can treat really well by inhibiting a single pathway target, HS is just not that simple,” Krueger said. Although largely an inflammatory process, the cascade of inflammatory factors for specific manifestations, such as tunnels, means that optimal therapy in one case might have little benefit in another.

The relatively new evidence that HS activity is not confined to lesional skin might be the most important recent step toward new strategies to target disease. These studies were performed by Kristina Navrazhina, MD, PhD, now a resident in dermatology at the Icahn School of Medicine at Mount Sinai, New York. She received her PhD while studying HS activity in non-lesional skin. Her work has led her to conclude that the best chance for better outcomes in HS is early diagnosis and treatment. Although this is generally true of any pathology, the changes in the HS phenotype once fistulae form includes a poor response to conventional therapies. 

In fact, based on her work in evaluating HS activity in non-lesional skin, Navrazhina has shown that “many patients with modest lesions already have advanced disease.” Consistent with the premise that HS is a deeply systemic inflammatory process, nodules, considered an early manifestation, turn out to be “the tip of the iceberg.”

 

Non-Lesional HS Skin Is Inflamed

When she has employed RNA sequencing based on tape strip sampling from completely normal skin away from nodules, interleukin (IL)-17 and a broad array of other inflammatory markers were found to be upregulated. When she performed ultrasound to look for disease activity under the normal skin, she has often found tunnels already formed. Doppler ultrasound showed some of these tunnels were actively draining.

This might provide a partial explanation for why therapies are not always effective even when clinical signs of disease are modest. 

“Are we missing the opportunity for intervening?” Navrazhina asked, noting that early intervention has been limited traditionally by extremely long diagnostic delays. Citing the literature, Navrazhina said the average delay is 7 years for HS versus 1 year for psoriasis. Patients often cycle through 3 or 4 providers before the diagnosis is made, she said.

Awakening first-line clinicians to the signs and symptoms of HS, whether in the emergency room or primary care, is a critical message because of the incrementally difficult task to control disease once fistulae have formed. 

Krueger made the same appeal. For the neutrophilic inflammation that characterizes nodules, targeted therapies are often effective, but he agreed that available therapies are generally far less so once tunnels form.

 

Role Seen for Bacteria in HS Pathogenesis

One reason might be an interaction between anaerobic bacteria and the keratinocytes that form the tunnel walls, according to Krueger. Although HS is not typically considered an infectious disease, he reported that the interaction of these bacteria with keratinocytes is associated with expression of approximately 1000 inflammatory gene products. The process of tunnel formation is traced to how factors recruited by upregulated inflammation, such as chemokines, coordinate.

He described recent work pursing novel strategies such as highly targeted antibiotics or inhibitors of complement factor C5a, which has been proposed as a biomarker for HS, to intervene in preventing or reversing HS tunnels. 

While this work progresses, one of the most Important unmet needs in HS is an accepted measure of clinically meaningful improvement in advanced disease, particularly the impact of therapy on HS tunnels, according to Krueger. 

“There is no measure of tunnel activity that the FDA accepts in evaluating drugs,” he noted, which will be essential for approving therapies that offer this benefit. 

A phase 3 trials program for one of the promising drugs, sonelokimab, was announced early in 2024. A nanobody that targets IL-17A/A, IL-17A/F, and IL-17F/F, the small size of this molecule permits exceptional tissue penetration while the broad anti-IL-17 activity has a high degree of theoretical potential in late-stage HS, according to Krueger. 

There are numerous pieces of the HS puzzle that are still missing, but both Krueger and Navrazhina are enthusiastic about new targets and opportunities for disease control that are stemming from a better understanding of the underlying pathophysiology. Not least, both indicated that testing for inflammatory phenotypes will allow for individualized therapeutic choices with a maximum likelihood of response, particularly if earlier diagnosis permits earlier treatment. 

“Due to the heterogeneity of HS, it is hard to know who will respond to which treatment or which treatment should be started first,” Navrazhina said. She thinks that early measures of the inflammatory profile in nodules or even non-lesional skin might provide that guidance. 

Both Krueger and Navrazhina reported no financial relationships relevant to this work. 

 

A version of this article appeared on Medscape.com.

NEW YORK, NY — Work over the past several years has reframed hidradenitis suppurativa (HS) as a large-field inflammatory process, a recharacterization that has immediate relevance to treatment strategies and goals, according to two investigators intimately involved in much of the recent progress.

“Success is being achieved by targeting multiple inflammatory axes in HS, and therapeutics are evolving rapidly,” reported James G. Krueger, MD, PhD, head of the Laboratory of Investigative Dermatology, Rockefeller University, New York, NY.

The activity of targeted anti-inflammatory therapies — bimekizumab just joined adalimumab and secukinumab as a third approved biologic for HS — is not news, but the degree to which inflammation is upregulated systemically, not just at areas of skin involvement, has changed the conceptualization of HS.

HS Is a Systemic Inflammatory Disease

Relative to psoriasis, for which there are many parallels, “HS is hugely more inflammatory in the systemic circulation,” Krueger said at the 27th Annual Winter Symposium — Advances in Medical and Surgical Dermatology (MSWS) 2024. Yet, HS is also more complex involving additional pathways that appear to include dysbiosis. The concept of follicular occlusion, once a common explanation for HS, has been left far behind.

“Unlike psoriasis, which we can treat really well by inhibiting a single pathway target, HS is just not that simple,” Krueger said. Although largely an inflammatory process, the cascade of inflammatory factors for specific manifestations, such as tunnels, means that optimal therapy in one case might have little benefit in another.

The relatively new evidence that HS activity is not confined to lesional skin might be the most important recent step toward new strategies to target disease. These studies were performed by Kristina Navrazhina, MD, PhD, now a resident in dermatology at the Icahn School of Medicine at Mount Sinai, New York. She received her PhD while studying HS activity in non-lesional skin. Her work has led her to conclude that the best chance for better outcomes in HS is early diagnosis and treatment. Although this is generally true of any pathology, the changes in the HS phenotype once fistulae form includes a poor response to conventional therapies. 

In fact, based on her work in evaluating HS activity in non-lesional skin, Navrazhina has shown that “many patients with modest lesions already have advanced disease.” Consistent with the premise that HS is a deeply systemic inflammatory process, nodules, considered an early manifestation, turn out to be “the tip of the iceberg.”

 

Non-Lesional HS Skin Is Inflamed

When she has employed RNA sequencing based on tape strip sampling from completely normal skin away from nodules, interleukin (IL)-17 and a broad array of other inflammatory markers were found to be upregulated. When she performed ultrasound to look for disease activity under the normal skin, she has often found tunnels already formed. Doppler ultrasound showed some of these tunnels were actively draining.

This might provide a partial explanation for why therapies are not always effective even when clinical signs of disease are modest. 

“Are we missing the opportunity for intervening?” Navrazhina asked, noting that early intervention has been limited traditionally by extremely long diagnostic delays. Citing the literature, Navrazhina said the average delay is 7 years for HS versus 1 year for psoriasis. Patients often cycle through 3 or 4 providers before the diagnosis is made, she said.

Awakening first-line clinicians to the signs and symptoms of HS, whether in the emergency room or primary care, is a critical message because of the incrementally difficult task to control disease once fistulae have formed. 

Krueger made the same appeal. For the neutrophilic inflammation that characterizes nodules, targeted therapies are often effective, but he agreed that available therapies are generally far less so once tunnels form.

 

Role Seen for Bacteria in HS Pathogenesis

One reason might be an interaction between anaerobic bacteria and the keratinocytes that form the tunnel walls, according to Krueger. Although HS is not typically considered an infectious disease, he reported that the interaction of these bacteria with keratinocytes is associated with expression of approximately 1000 inflammatory gene products. The process of tunnel formation is traced to how factors recruited by upregulated inflammation, such as chemokines, coordinate.

He described recent work pursing novel strategies such as highly targeted antibiotics or inhibitors of complement factor C5a, which has been proposed as a biomarker for HS, to intervene in preventing or reversing HS tunnels. 

While this work progresses, one of the most Important unmet needs in HS is an accepted measure of clinically meaningful improvement in advanced disease, particularly the impact of therapy on HS tunnels, according to Krueger. 

“There is no measure of tunnel activity that the FDA accepts in evaluating drugs,” he noted, which will be essential for approving therapies that offer this benefit. 

A phase 3 trials program for one of the promising drugs, sonelokimab, was announced early in 2024. A nanobody that targets IL-17A/A, IL-17A/F, and IL-17F/F, the small size of this molecule permits exceptional tissue penetration while the broad anti-IL-17 activity has a high degree of theoretical potential in late-stage HS, according to Krueger. 

There are numerous pieces of the HS puzzle that are still missing, but both Krueger and Navrazhina are enthusiastic about new targets and opportunities for disease control that are stemming from a better understanding of the underlying pathophysiology. Not least, both indicated that testing for inflammatory phenotypes will allow for individualized therapeutic choices with a maximum likelihood of response, particularly if earlier diagnosis permits earlier treatment. 

“Due to the heterogeneity of HS, it is hard to know who will respond to which treatment or which treatment should be started first,” Navrazhina said. She thinks that early measures of the inflammatory profile in nodules or even non-lesional skin might provide that guidance. 

Both Krueger and Navrazhina reported no financial relationships relevant to this work. 

 

A version of this article appeared on Medscape.com.