Clinician Reviews

TOPLINE:

The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.

METHODOLOGY:

• MDA5 antibody-positive DM is a rare DM subtype associated with ILD, which is categorized into rapidly progressive ILD (RPILD) and chronic ILD, with the former having a particularly high mortality rate.
• In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
• The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.

TAKEAWAY:

• Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
• ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
• The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
• Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.

IN PRACTICE:

“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.

SOURCE:

This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.

LIMITATIONS:

Study limitations were the study’s retrospective design and small sample size.

DISCLOSURES:

No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.

METHODOLOGY:

• MDA5 antibody-positive DM is a rare DM subtype associated with ILD, which is categorized into rapidly progressive ILD (RPILD) and chronic ILD, with the former having a particularly high mortality rate.
• In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
• The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.

TAKEAWAY:

• Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
• ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
• The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
• Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.

IN PRACTICE:

“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.

SOURCE:

This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.

LIMITATIONS:

Study limitations were the study’s retrospective design and small sample size.

DISCLOSURES:

No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.

METHODOLOGY:

• MDA5 antibody-positive DM is a rare DM subtype associated with ILD, which is categorized into rapidly progressive ILD (RPILD) and chronic ILD, with the former having a particularly high mortality rate.
• In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
• The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.

TAKEAWAY:

• Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
• ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
• The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
• Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.

IN PRACTICE:

“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.

SOURCE:

This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.

LIMITATIONS:

Study limitations were the study’s retrospective design and small sample size.

DISCLOSURES:

No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.

A version of this article appeared on Medscape.com.

BY DEEPA VARMA

TOPLINE:

In patients with polycystic ovary syndrome (PCOS), laser and light therapies, alone or in combination with pharmacological agents, improve hirsutism and psychological well-being in women, according to the results of a systematic review.

METHODOLOGY:

• Hirsutism, which affects 70%-80% of women with PCOS, is frequently marginalized as a cosmetic issue by healthcare providers, despite its significant psychological repercussions, including diminished self-esteem, reduced quality of life, and heightened depression.
• The 2023 international evidence-based PCOS guideline considers managing hirsutism a priority in women with PCOS.
• Researchers reviewed six studies (four randomized controlled trials and two cohort studies), which included 423 patients with PCOS who underwent laser or light-based hair reduction therapies, published through 2022.
• The studies evaluated the alexandrite laser, diode laser, and intense pulsed light (IPL) therapy, with and without pharmacological treatments. The main outcomes were hirsutism severity, psychological outcome, and adverse events.

TAKEAWAY:

• Alexandrite laser (wavelength, 755 nm) showed effective hair reduction and improved patient satisfaction (one study); high-fluence treatment yielded better outcomes than low-fluence treatment (one study). Alexandrite laser 755 nm also showed longer hair-free intervals and greater hair reduction than IPL therapy at 650-1000 nm (one study).
• Combined IPL (600 nm) and metformin therapy improved hirsutism and hair count reduction compared with IPL alone, but with more side effects (one study).
• Diode laser treatments (810 nm) with combined oral contraceptives improved hirsutism and related quality of life measures compared with diode laser alone or with metformin (one study).
• Comparing two diode lasers (wavelengths, 810 nm), low-fluence, high repetition laser showed superior hair width reduction and lower pain scores than high fluence, low-repetition laser (one study).

IN PRACTICE:

Laser and light treatments alone or combined with other treatments have demonstrated “encouraging results in reducing hirsutism severity, enhancing psychological well-being, and improving overall quality of life for affected individuals,” the authors wrote, noting that additional high-quality trials evaluating these treatments, which include more patients with different skin tones, are needed.

SOURCE:

The first author of the review is Katrina Tan, MD, Monash Health, Department of Dermatology, Melbourne, Victoria, Australia, and it was published online in JAMA Dermatology.

LIMITATIONS:

Limitations include low certainty of evidence because of the observational nature of some of the studies, the small number of studies, and underrepresentation of darker skin types, limiting generalizability.

DISCLOSURES:

The review is part of an update to the PCOS guideline, which was funded by the Australian National Health and Medical Research Council through various organizations. Several authors reported receiving grants and personal fees outside this work. Dr. Tan was a member of the 2023 PCOS guideline evidence team. Other authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

BY DEEPA VARMA

TOPLINE:

In patients with polycystic ovary syndrome (PCOS), laser and light therapies, alone or in combination with pharmacological agents, improve hirsutism and psychological well-being in women, according to the results of a systematic review.

METHODOLOGY:

• Hirsutism, which affects 70%-80% of women with PCOS, is frequently marginalized as a cosmetic issue by healthcare providers, despite its significant psychological repercussions, including diminished self-esteem, reduced quality of life, and heightened depression.
• The 2023 international evidence-based PCOS guideline considers managing hirsutism a priority in women with PCOS.
• Researchers reviewed six studies (four randomized controlled trials and two cohort studies), which included 423 patients with PCOS who underwent laser or light-based hair reduction therapies, published through 2022.
• The studies evaluated the alexandrite laser, diode laser, and intense pulsed light (IPL) therapy, with and without pharmacological treatments. The main outcomes were hirsutism severity, psychological outcome, and adverse events.

TAKEAWAY:

• Alexandrite laser (wavelength, 755 nm) showed effective hair reduction and improved patient satisfaction (one study); high-fluence treatment yielded better outcomes than low-fluence treatment (one study). Alexandrite laser 755 nm also showed longer hair-free intervals and greater hair reduction than IPL therapy at 650-1000 nm (one study).
• Combined IPL (600 nm) and metformin therapy improved hirsutism and hair count reduction compared with IPL alone, but with more side effects (one study).
• Diode laser treatments (810 nm) with combined oral contraceptives improved hirsutism and related quality of life measures compared with diode laser alone or with metformin (one study).
• Comparing two diode lasers (wavelengths, 810 nm), low-fluence, high repetition laser showed superior hair width reduction and lower pain scores than high fluence, low-repetition laser (one study).

IN PRACTICE:

Laser and light treatments alone or combined with other treatments have demonstrated “encouraging results in reducing hirsutism severity, enhancing psychological well-being, and improving overall quality of life for affected individuals,” the authors wrote, noting that additional high-quality trials evaluating these treatments, which include more patients with different skin tones, are needed.

SOURCE:

The first author of the review is Katrina Tan, MD, Monash Health, Department of Dermatology, Melbourne, Victoria, Australia, and it was published online in JAMA Dermatology.

LIMITATIONS:

Limitations include low certainty of evidence because of the observational nature of some of the studies, the small number of studies, and underrepresentation of darker skin types, limiting generalizability.

DISCLOSURES:

The review is part of an update to the PCOS guideline, which was funded by the Australian National Health and Medical Research Council through various organizations. Several authors reported receiving grants and personal fees outside this work. Dr. Tan was a member of the 2023 PCOS guideline evidence team. Other authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

BY DEEPA VARMA

TOPLINE:

In patients with polycystic ovary syndrome (PCOS), laser and light therapies, alone or in combination with pharmacological agents, improve hirsutism and psychological well-being in women, according to the results of a systematic review.

METHODOLOGY:

• Hirsutism, which affects 70%-80% of women with PCOS, is frequently marginalized as a cosmetic issue by healthcare providers, despite its significant psychological repercussions, including diminished self-esteem, reduced quality of life, and heightened depression.
• The 2023 international evidence-based PCOS guideline considers managing hirsutism a priority in women with PCOS.
• Researchers reviewed six studies (four randomized controlled trials and two cohort studies), which included 423 patients with PCOS who underwent laser or light-based hair reduction therapies, published through 2022.
• The studies evaluated the alexandrite laser, diode laser, and intense pulsed light (IPL) therapy, with and without pharmacological treatments. The main outcomes were hirsutism severity, psychological outcome, and adverse events.

TAKEAWAY:

• Alexandrite laser (wavelength, 755 nm) showed effective hair reduction and improved patient satisfaction (one study); high-fluence treatment yielded better outcomes than low-fluence treatment (one study). Alexandrite laser 755 nm also showed longer hair-free intervals and greater hair reduction than IPL therapy at 650-1000 nm (one study).
• Combined IPL (600 nm) and metformin therapy improved hirsutism and hair count reduction compared with IPL alone, but with more side effects (one study).
• Diode laser treatments (810 nm) with combined oral contraceptives improved hirsutism and related quality of life measures compared with diode laser alone or with metformin (one study).
• Comparing two diode lasers (wavelengths, 810 nm), low-fluence, high repetition laser showed superior hair width reduction and lower pain scores than high fluence, low-repetition laser (one study).

IN PRACTICE:

Laser and light treatments alone or combined with other treatments have demonstrated “encouraging results in reducing hirsutism severity, enhancing psychological well-being, and improving overall quality of life for affected individuals,” the authors wrote, noting that additional high-quality trials evaluating these treatments, which include more patients with different skin tones, are needed.

SOURCE:

The first author of the review is Katrina Tan, MD, Monash Health, Department of Dermatology, Melbourne, Victoria, Australia, and it was published online in JAMA Dermatology.

LIMITATIONS:

Limitations include low certainty of evidence because of the observational nature of some of the studies, the small number of studies, and underrepresentation of darker skin types, limiting generalizability.

DISCLOSURES:

The review is part of an update to the PCOS guideline, which was funded by the Australian National Health and Medical Research Council through various organizations. Several authors reported receiving grants and personal fees outside this work. Dr. Tan was a member of the 2023 PCOS guideline evidence team. Other authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Results from a preliminary clinical trial demonstrated the obesity drug, tirzepatide, effectively treated obstructive sleep apnea (OSA), according to information sent to investors of the pharmaceutical company, Eli Lilly.

Indiana-based Eli Lilly sells tirzepatide under the brand name Zepbound, which was approved by the FDA in November to treat overweight and obesity. Tirzepatide is also marketed under the name Mounjaro to treat diabetes, and it’s among the same class of drugs as other well-known weight loss and diabetes drugs like Ozempic and Wegovy.

The newly announced results came from a pair of studies that followed people with moderate to severe OSA who also had obesity. People in the study took tirzepatide, which is given by injection, for one year. One study evaluated people who were using CPAP during sleep, and another study included people who didn’t use the device. People in both studies taking tirzepatide had significant reductions in sleep events and also lost about 20% of body weight. About 70% of people in the studies were men.

The findings have not yet been published in a peer-reviewed medical journal, and the preliminary results were announced by Eli Lilly because of reporting requirements related to information that could affect stock prices. The company indicated that detailed results will be presented at a conference of the American Diabetes Association in June and will be submitted to a peer-reviewed journal for consideration of publication. The company also plans to submit the information to the FDA for approval consideration mid-year, the investor news release stated.

People in the study taking tirzepatide on average experienced 63% fewer instances of reduced oxygen due to breathing changes, or events when breathing entirely stopped, Eli Lilly reported.

A sleep expert from Washington University in St. Louis told The New York Times the initial findings were extremely positive and noted that tirzepatide works to treat the underlying cause of sleep apnea, rather than current treatments that just address symptoms.

Tirzepatide “is a great alternative for people who are obese and can’t use CPAP or are on CPAP and want to improve the effect,” Eric Landsness, MD, PhD, told The New York Times. 

Eli Lilly indicated the most commonly reported adverse events in the studies were diarrhea, nausea, vomiting, and constipation.

An estimated 39 million people have OSA and about 33 million people use CPAP machines, according to The National Council on Aging. The condition has been increasingly diagnosed in recent years and becomes more likely to affect people as they get older.

A version of this article appeared on WebMD.com.

Results from a preliminary clinical trial demonstrated the obesity drug, tirzepatide, effectively treated obstructive sleep apnea (OSA), according to information sent to investors of the pharmaceutical company, Eli Lilly.

Indiana-based Eli Lilly sells tirzepatide under the brand name Zepbound, which was approved by the FDA in November to treat overweight and obesity. Tirzepatide is also marketed under the name Mounjaro to treat diabetes, and it’s among the same class of drugs as other well-known weight loss and diabetes drugs like Ozempic and Wegovy.

The newly announced results came from a pair of studies that followed people with moderate to severe OSA who also had obesity. People in the study took tirzepatide, which is given by injection, for one year. One study evaluated people who were using CPAP during sleep, and another study included people who didn’t use the device. People in both studies taking tirzepatide had significant reductions in sleep events and also lost about 20% of body weight. About 70% of people in the studies were men.

The findings have not yet been published in a peer-reviewed medical journal, and the preliminary results were announced by Eli Lilly because of reporting requirements related to information that could affect stock prices. The company indicated that detailed results will be presented at a conference of the American Diabetes Association in June and will be submitted to a peer-reviewed journal for consideration of publication. The company also plans to submit the information to the FDA for approval consideration mid-year, the investor news release stated.

People in the study taking tirzepatide on average experienced 63% fewer instances of reduced oxygen due to breathing changes, or events when breathing entirely stopped, Eli Lilly reported.

A sleep expert from Washington University in St. Louis told The New York Times the initial findings were extremely positive and noted that tirzepatide works to treat the underlying cause of sleep apnea, rather than current treatments that just address symptoms.

Tirzepatide “is a great alternative for people who are obese and can’t use CPAP or are on CPAP and want to improve the effect,” Eric Landsness, MD, PhD, told The New York Times. 

Eli Lilly indicated the most commonly reported adverse events in the studies were diarrhea, nausea, vomiting, and constipation.

An estimated 39 million people have OSA and about 33 million people use CPAP machines, according to The National Council on Aging. The condition has been increasingly diagnosed in recent years and becomes more likely to affect people as they get older.

A version of this article appeared on WebMD.com.

Results from a preliminary clinical trial demonstrated the obesity drug, tirzepatide, effectively treated obstructive sleep apnea (OSA), according to information sent to investors of the pharmaceutical company, Eli Lilly.

Indiana-based Eli Lilly sells tirzepatide under the brand name Zepbound, which was approved by the FDA in November to treat overweight and obesity. Tirzepatide is also marketed under the name Mounjaro to treat diabetes, and it’s among the same class of drugs as other well-known weight loss and diabetes drugs like Ozempic and Wegovy.

The newly announced results came from a pair of studies that followed people with moderate to severe OSA who also had obesity. People in the study took tirzepatide, which is given by injection, for one year. One study evaluated people who were using CPAP during sleep, and another study included people who didn’t use the device. People in both studies taking tirzepatide had significant reductions in sleep events and also lost about 20% of body weight. About 70% of people in the studies were men.

The findings have not yet been published in a peer-reviewed medical journal, and the preliminary results were announced by Eli Lilly because of reporting requirements related to information that could affect stock prices. The company indicated that detailed results will be presented at a conference of the American Diabetes Association in June and will be submitted to a peer-reviewed journal for consideration of publication. The company also plans to submit the information to the FDA for approval consideration mid-year, the investor news release stated.

People in the study taking tirzepatide on average experienced 63% fewer instances of reduced oxygen due to breathing changes, or events when breathing entirely stopped, Eli Lilly reported.

A sleep expert from Washington University in St. Louis told The New York Times the initial findings were extremely positive and noted that tirzepatide works to treat the underlying cause of sleep apnea, rather than current treatments that just address symptoms.

Tirzepatide “is a great alternative for people who are obese and can’t use CPAP or are on CPAP and want to improve the effect,” Eric Landsness, MD, PhD, told The New York Times. 

Eli Lilly indicated the most commonly reported adverse events in the studies were diarrhea, nausea, vomiting, and constipation.

An estimated 39 million people have OSA and about 33 million people use CPAP machines, according to The National Council on Aging. The condition has been increasingly diagnosed in recent years and becomes more likely to affect people as they get older.

A version of this article appeared on WebMD.com.

A mix of microbes may help explain why some people develop dry eye disease, new research showed.

This finding suggests that bacteria may cause dry eye and could someday point to new treatments for the condition and related disorders, which affect an estimated 27 million Americans, according to researchers.

Current treatments aim to preserve and enhance tears and tear production to ease the grittiness and itchiness that accompany dry eye disease. 

To examine the role of the ocular microbiome in dry eye disease, scientists in Texas analyzed swab samples from 30 men and women, nine of whom had dry eye.

They found Streptococcus and Pedobacter species were the most common bacteria in healthy eyes.

In people with dry eye, however, more Acinetobacter species were detected.

“We think the metabolites produced by these bacteria are responsible for dry eye conditions,” study coauthor Pallavi Sharma said in a news release about the findings. 

Sharma, a graduate student at Stephen F. Austin State University in Nacogdoches, Texas, presented this research last month at the annual meeting of the American Society for Biochemistry and Molecular Biology. The research team was led by Alexandra Van Kley, PhD, a professor of biology at the university.

“Once we understand the eye microbiota properly, it will improve disease diagnosis at an early stage,” Van Kley predicted in the news release. “This knowledge can also serve as a catalyst for developing innovative therapies aimed at preventing and treating ocular disease as well as those that affect the central microbiome site: The gut.”

Investigators in Australia have conducted similar experiments in patients with meibomian gland dysfunction, a condition marked by underproduction of key oils in the eye.

One group reported in August 2023 the finding of “detectable differences in the bacterial richness, diversity, and community structure of the conjunctiva and eyelid margin between individuals with meibomian gland dysfunction with and without lacrimal dysfunction, as well as to healthy controls.”

More research is needed to confirm and understand the findings, though, and “to determine if manipulating the microbiome could be a potential treatment for the condition,” they wrote.

A version of this article appeared on Medscape.com.

A mix of microbes may help explain why some people develop dry eye disease, new research showed.

This finding suggests that bacteria may cause dry eye and could someday point to new treatments for the condition and related disorders, which affect an estimated 27 million Americans, according to researchers.

Current treatments aim to preserve and enhance tears and tear production to ease the grittiness and itchiness that accompany dry eye disease. 

To examine the role of the ocular microbiome in dry eye disease, scientists in Texas analyzed swab samples from 30 men and women, nine of whom had dry eye.

They found Streptococcus and Pedobacter species were the most common bacteria in healthy eyes.

In people with dry eye, however, more Acinetobacter species were detected.

“We think the metabolites produced by these bacteria are responsible for dry eye conditions,” study coauthor Pallavi Sharma said in a news release about the findings. 

Sharma, a graduate student at Stephen F. Austin State University in Nacogdoches, Texas, presented this research last month at the annual meeting of the American Society for Biochemistry and Molecular Biology. The research team was led by Alexandra Van Kley, PhD, a professor of biology at the university.

“Once we understand the eye microbiota properly, it will improve disease diagnosis at an early stage,” Van Kley predicted in the news release. “This knowledge can also serve as a catalyst for developing innovative therapies aimed at preventing and treating ocular disease as well as those that affect the central microbiome site: The gut.”

Investigators in Australia have conducted similar experiments in patients with meibomian gland dysfunction, a condition marked by underproduction of key oils in the eye.

One group reported in August 2023 the finding of “detectable differences in the bacterial richness, diversity, and community structure of the conjunctiva and eyelid margin between individuals with meibomian gland dysfunction with and without lacrimal dysfunction, as well as to healthy controls.”

More research is needed to confirm and understand the findings, though, and “to determine if manipulating the microbiome could be a potential treatment for the condition,” they wrote.

A version of this article appeared on Medscape.com.

A mix of microbes may help explain why some people develop dry eye disease, new research showed.

This finding suggests that bacteria may cause dry eye and could someday point to new treatments for the condition and related disorders, which affect an estimated 27 million Americans, according to researchers.

Current treatments aim to preserve and enhance tears and tear production to ease the grittiness and itchiness that accompany dry eye disease. 

To examine the role of the ocular microbiome in dry eye disease, scientists in Texas analyzed swab samples from 30 men and women, nine of whom had dry eye.

They found Streptococcus and Pedobacter species were the most common bacteria in healthy eyes.

In people with dry eye, however, more Acinetobacter species were detected.

“We think the metabolites produced by these bacteria are responsible for dry eye conditions,” study coauthor Pallavi Sharma said in a news release about the findings. 

Sharma, a graduate student at Stephen F. Austin State University in Nacogdoches, Texas, presented this research last month at the annual meeting of the American Society for Biochemistry and Molecular Biology. The research team was led by Alexandra Van Kley, PhD, a professor of biology at the university.

“Once we understand the eye microbiota properly, it will improve disease diagnosis at an early stage,” Van Kley predicted in the news release. “This knowledge can also serve as a catalyst for developing innovative therapies aimed at preventing and treating ocular disease as well as those that affect the central microbiome site: The gut.”

Investigators in Australia have conducted similar experiments in patients with meibomian gland dysfunction, a condition marked by underproduction of key oils in the eye.

One group reported in August 2023 the finding of “detectable differences in the bacterial richness, diversity, and community structure of the conjunctiva and eyelid margin between individuals with meibomian gland dysfunction with and without lacrimal dysfunction, as well as to healthy controls.”

More research is needed to confirm and understand the findings, though, and “to determine if manipulating the microbiome could be a potential treatment for the condition,” they wrote.

A version of this article appeared on Medscape.com.

SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.

“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”

LucaLorenzelli/Thinkstock

Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:

Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.

As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”

Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”

He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.


 

Courtesy University of California, San Diego

Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”

Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.

Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”

Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”

Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.

SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.

“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”

LucaLorenzelli/Thinkstock

Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:

Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.

As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”

Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”

He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.


 

Courtesy University of California, San Diego

Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”

Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.

Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”

Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”

Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.

SAN DIEGO — Whether you completed your dermatology residency training 20 years ago or 2 years ago, recent advances in treatments for atopic dermatitis (AD) have likely influenced your “go to” interventions when treating children with AD, according to Lawrence F. Eichenfield, MD.

“There have been many changes in the understanding of AD and recognition of the variable courses of the disease, and the associated allergic and nonallergic comorbidities,” Dr. Eichenfield, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego in California, said at the Society for Pediatric Dermatology meeting, held the day before the annual meeting of the American Academy of Dermatology. “With our revolutionary systemic and evolving topical therapies, we are in a new day of pediatric management.”

LucaLorenzelli/Thinkstock

Drawing from 2023 American Academy of Dermatology guidelines of care on topical treatments of AD and his own clinical experience, he shared his perspective on “what’s tried and true” in care for patients with persistent eczema:

Both bathing and moisturizing leave skin moist. It’s well established that the use of moisturizers/emollients minimizes xerosis and the amount of prescription anti-inflammatory medications, but limited evidence exists to recommend a particular ingredient and formulation, said Dr. Eichenfield, also professor of dermatology and pediatrics at the University of California, San Diego. “Future studies may tell us whether specific moisturizers work better than others, and/or if early interventions may prevent AD, but that remains a big question mark,” he noted. In addition, applications may sometimes “mobilize” topical prescriptive residual absorption and activity.

As for baths, he said, “avoidance of bathing to avoid drying out skin is a practice without evidence basis. Bathing also may have many benefits in active eczema.”

Bleach baths may enhance skin barrier function, reduce itch, and improve eczema, but the practice remains controversial, he continued. Authors of a systematic review and meta-analysis concluded that while bleach baths are effective in reducing the severity of AD, they do not appear to be more effective than water bath alone. Authors of a more recent study found that bleach baths did not normalize dysbiosis, “but that study did not compare outcomes to bathing without bleach,” Dr. Eichenfield noted.“My sense is there is some benefit to regular bathing, especially in children with moderate to severe AD, especially those with colonized or infected eczema.”

He advises clinicians to be aware of other “standard AD interventions” from around the world, including black tea wet dressings and green tea bath therapy.


 

Courtesy University of California, San Diego

Topical corticosteroids. These are “tried and true” for their anti-inflammatory properties and rapid response, relatively low cost, and large range of potency, he said. Potential problems include the burden of topical application and the potential for stinging/burning, atrophy, telangiectasias, adrenal axis suppression, and concerns about withdrawal phenomena. “Being a proponent of topical corticosteroids, but explaining reasonable and appropriate use can be challenging,” Dr. Eichenfield said. “Social media has influenced concerns about topical corticosteroids, with steroid addiction and withdrawal being concerns influencing discomfort with therapies.”

Make sure to measure outcomes. The suggested core outcome measure for recording clinical signs in AD clinical trials is the Eczema Area and Severity Index (EASI) score, he said. In clinical practice, Dr. Eichenfield favors body surface area (BSA) and the Validated Global Assessment scale (v-IGA) to measure signs of moderate to severe AD. “Documenting extent of disease makes a big difference in families understanding how severe their child’s disease is and how it is doing over time.” Alternatively, he recommends the Atopic Dermatitis Control Tool (ADCT) or the Recap of Atopic Eczema (RECAP) as tools assessing long-term disease control.

Familiarize yourself with nonsteroidal anti-inflammatory medications for care regimens. Options include topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus; phosphodiesterase 4 (PDE-4) inhibitors such as crisaborole and roflumilast; the aryl-hydrocarbon receptor agonist tapinarof; and topical Janus kinase (JAK) inhibitors such as delgocitinib and ruxolitinib as well as others in development. “There is variable status around the world in terms of whether these nonsteroidal options are approved or not,” Dr. Eichenfield said. “Issues of use include cost, availability, side effects, and concerns about potential absorption. I think there’s an evolution in how much we rely on these instead of topical corticosteroids. They’re more commonly used in maintenance regimens rather than for remission induction.”

Dr. Eichenfield encouraged dermatologists to share information about and experiences with evolving treatment options for AD, “because when the studies are done, they are done as monotherapy. We must translate that into clinical practice and figure out how they fit in. Our exchange of information is critical.”

Dr. Eichenfield disclosed conflicts of interest from many pharmaceutical companies, including those with AD treatments.

SAN DIEGO — Compared with the use of topical minoxidil for hair loss, the used of low-dose oral minoxidil (LDOM) can be considered when topical minoxidil is more expensive or logistically challenging, has plateaued in efficacy, leaves unwanted product residue, causes skin irritation, or exacerbates the inflammatory process.

Those are among the key recommendations that resulted from a modified eDelphi consensus of experts who convened to develop guidelines for LDOM prescribing and monitoring.

“Topical minoxidil is safe, effective, over-the-counter, and FDA-approved to treat the most common form of hair loss, androgenetic alopecia,” one of the study authors, Jennifer Fu, MD, a dermatologist who directs the Hair Disorders Clinic at the University of California, San Francisco, told this news organization following the annual meeting of the American Academy of Dermatology. The results of the expert consensus were presented during a poster session at the meeting. “It is often used off label for other types of hair loss, yet clinicians who treat hair loss know that patient compliance with topical minoxidil can be poor for a variety of reasons,” she said. “Patients report that it can be difficult to apply and complicate hair styling. For many patients, topical minoxidil can be drying or cause irritant or allergic contact reactions.”

Dr. Fu

LDOM has become a popular alternative for patients for whom topical minoxidil is logistically challenging, irritating, or ineffective, she continued. Although oral minoxidil is no longer a first-line antihypertensive agent given the risk of cardiovascular adverse effects at higher antihypertensive dosing (10-40 mg daily), a growing number of small studies have documented the use of LDOM at doses ranging from 0.25 mg to 5 mg daily as a safe, effective option for various types of hair loss.

“Given the current absence of larger trials on this topic, our research group identified a need for expert-based guidelines for prescribing and monitoring LDOM use in hair loss patients,” Dr. Fu said. “Our goal was to provide clinicians who treat hair loss patients a road map for using LDOM effectively, maximizing hair growth, and minimizing potential cardiovascular adverse effects.”


 

Arriving at a Consensus

The process involved 43 hair loss specialists from 12 countries with an average of 6.29 years of experience with LDOM for hair loss, who participated in a multi-round modified Delphi process. They considered questions that addressed LDOM safety, efficacy, dosing, and monitoring for hair loss, and consensus was reached if at least 70% of participants indicated “agree” or “strongly agree” on a five-point Likert scale. Round 1 consisted of 180 open-ended, multiple-choice, or Likert-scale questions, while round 2 involved 121 Likert-scale questions, round 3 consisted of 16 Likert-scale questions, and round 4 included 11 Likert-scale questions. In all, 94 items achieved Likert-scale consensus.

Specifically, experts on the panel found a direct benefit of LDOM for androgenetic alopecia, age-related patterned thinning, alopecia areata, telogen effluvium, traction alopecia, persistent chemotherapy-induced alopecia, and endocrine therapy-induced alopecia. They found a supportive benefit of LDOM for lichen planopilaris, frontal fibrosing alopecia, central centrifugal alopecia, and fibrosing alopecia in a patterned distribution.

“LDOM can be considered when topical minoxidil is more expensive, logistically challenging, has plateaued in efficacy, results in undesirable product residue/skin irritation,” or exacerbates inflammatory processes (ie eczema, psoriasis), they added.

Contraindications to LDOM listed in the consensus recommendations include hypersensitivity to minoxidil, significant drug-drug interactions with LDOM, a history of pericardial effusion/tamponade, pericarditis, heart failure, pulmonary hypertension associated with mitral stenosis, pheochromocytoma, and pregnancy/breastfeeding. Cited precautions of LDOM use include a history of tachycardia or arrhythmia, hypotension, renal impairment, and being on dialysis.

Dr. Fu and colleagues noted that the earliest time point at which LDOM should be expected to demonstrate efficacy is 3-6 months. “Baseline testing is not routine but may be considered in case of identified precautions,” they wrote. They also noted that LDOM can possibly be co-administered with beta-blockers with a specialty consultation, and with spironolactone in biologic female or transgender female patients with hirsutism, acne, polycystic ovary syndrome (PCOS), and with lower extremity and facial edema.

According to the consensus statement, the most frequently prescribed LDOM dosing regimen in adult females aged 18 years and older includes a starting dose of 1.25 mg daily, with a dosing range between 0.625 mg and 5 mg daily. For adult males, the most frequently prescribed dosing regimen is a starting dose of 2.5 daily, with a dosing range between 1.25 mg and 5 mg daily. The most frequently prescribed LDOM dosing regimen in adolescent females aged 12-17 years is a starting dose of 0.625 mg daily, with a dosing range of 0.625 to 2.5 mg daily. For adolescent males, the recommended regimen is a starting dose of 1.25 mg daily, with a dosing range of 1.25 mg to 5 mg daily.

“We hope that this consensus statement will guide our colleagues who would like to use LDOM to treat hair loss in their adult and adolescent patients,” Dr. Fu told this news organization. “These recommendations may be used to inform clinical practice until additional evidence-based data becomes available.”

She acknowledged certain limitations of the effort, including the fact that the expert panel was underrepresented in treating hair loss in pediatric patients, “and therefore failed to reach consensus on LDOM pediatric use and dosing,” she said. “We encourage our pediatric dermatology colleagues to further research LDOM in pediatric patients.”

In an interview, Shari Lipner, MD, PhD, associate professor of clinical dermatology, Weill Cornell Medicine, New York, who was asked to comment, but was not involved with the work, characterized the consensus as a “helpful, concise reference guide for dermatologists.”

Dr. Lipner

The advantages of the study are the standardized methods used, “and the experience of the panel,” she said. “Study limitations include the response rate, which was less than 60%, and the risk of potential side effects are not stratified by age, sex, or comorbidities,” she added.

Dr. Fu disclosed that she is a consultant to Pfizer. Dr. Lipner reported having no relevant disclosures.

SAN DIEGO — Compared with the use of topical minoxidil for hair loss, the used of low-dose oral minoxidil (LDOM) can be considered when topical minoxidil is more expensive or logistically challenging, has plateaued in efficacy, leaves unwanted product residue, causes skin irritation, or exacerbates the inflammatory process.

Those are among the key recommendations that resulted from a modified eDelphi consensus of experts who convened to develop guidelines for LDOM prescribing and monitoring.

“Topical minoxidil is safe, effective, over-the-counter, and FDA-approved to treat the most common form of hair loss, androgenetic alopecia,” one of the study authors, Jennifer Fu, MD, a dermatologist who directs the Hair Disorders Clinic at the University of California, San Francisco, told this news organization following the annual meeting of the American Academy of Dermatology. The results of the expert consensus were presented during a poster session at the meeting. “It is often used off label for other types of hair loss, yet clinicians who treat hair loss know that patient compliance with topical minoxidil can be poor for a variety of reasons,” she said. “Patients report that it can be difficult to apply and complicate hair styling. For many patients, topical minoxidil can be drying or cause irritant or allergic contact reactions.”

Dr. Fu

LDOM has become a popular alternative for patients for whom topical minoxidil is logistically challenging, irritating, or ineffective, she continued. Although oral minoxidil is no longer a first-line antihypertensive agent given the risk of cardiovascular adverse effects at higher antihypertensive dosing (10-40 mg daily), a growing number of small studies have documented the use of LDOM at doses ranging from 0.25 mg to 5 mg daily as a safe, effective option for various types of hair loss.

“Given the current absence of larger trials on this topic, our research group identified a need for expert-based guidelines for prescribing and monitoring LDOM use in hair loss patients,” Dr. Fu said. “Our goal was to provide clinicians who treat hair loss patients a road map for using LDOM effectively, maximizing hair growth, and minimizing potential cardiovascular adverse effects.”


 

Arriving at a Consensus

The process involved 43 hair loss specialists from 12 countries with an average of 6.29 years of experience with LDOM for hair loss, who participated in a multi-round modified Delphi process. They considered questions that addressed LDOM safety, efficacy, dosing, and monitoring for hair loss, and consensus was reached if at least 70% of participants indicated “agree” or “strongly agree” on a five-point Likert scale. Round 1 consisted of 180 open-ended, multiple-choice, or Likert-scale questions, while round 2 involved 121 Likert-scale questions, round 3 consisted of 16 Likert-scale questions, and round 4 included 11 Likert-scale questions. In all, 94 items achieved Likert-scale consensus.

Specifically, experts on the panel found a direct benefit of LDOM for androgenetic alopecia, age-related patterned thinning, alopecia areata, telogen effluvium, traction alopecia, persistent chemotherapy-induced alopecia, and endocrine therapy-induced alopecia. They found a supportive benefit of LDOM for lichen planopilaris, frontal fibrosing alopecia, central centrifugal alopecia, and fibrosing alopecia in a patterned distribution.

“LDOM can be considered when topical minoxidil is more expensive, logistically challenging, has plateaued in efficacy, results in undesirable product residue/skin irritation,” or exacerbates inflammatory processes (ie eczema, psoriasis), they added.

Contraindications to LDOM listed in the consensus recommendations include hypersensitivity to minoxidil, significant drug-drug interactions with LDOM, a history of pericardial effusion/tamponade, pericarditis, heart failure, pulmonary hypertension associated with mitral stenosis, pheochromocytoma, and pregnancy/breastfeeding. Cited precautions of LDOM use include a history of tachycardia or arrhythmia, hypotension, renal impairment, and being on dialysis.

Dr. Fu and colleagues noted that the earliest time point at which LDOM should be expected to demonstrate efficacy is 3-6 months. “Baseline testing is not routine but may be considered in case of identified precautions,” they wrote. They also noted that LDOM can possibly be co-administered with beta-blockers with a specialty consultation, and with spironolactone in biologic female or transgender female patients with hirsutism, acne, polycystic ovary syndrome (PCOS), and with lower extremity and facial edema.

According to the consensus statement, the most frequently prescribed LDOM dosing regimen in adult females aged 18 years and older includes a starting dose of 1.25 mg daily, with a dosing range between 0.625 mg and 5 mg daily. For adult males, the most frequently prescribed dosing regimen is a starting dose of 2.5 daily, with a dosing range between 1.25 mg and 5 mg daily. The most frequently prescribed LDOM dosing regimen in adolescent females aged 12-17 years is a starting dose of 0.625 mg daily, with a dosing range of 0.625 to 2.5 mg daily. For adolescent males, the recommended regimen is a starting dose of 1.25 mg daily, with a dosing range of 1.25 mg to 5 mg daily.

“We hope that this consensus statement will guide our colleagues who would like to use LDOM to treat hair loss in their adult and adolescent patients,” Dr. Fu told this news organization. “These recommendations may be used to inform clinical practice until additional evidence-based data becomes available.”

She acknowledged certain limitations of the effort, including the fact that the expert panel was underrepresented in treating hair loss in pediatric patients, “and therefore failed to reach consensus on LDOM pediatric use and dosing,” she said. “We encourage our pediatric dermatology colleagues to further research LDOM in pediatric patients.”

In an interview, Shari Lipner, MD, PhD, associate professor of clinical dermatology, Weill Cornell Medicine, New York, who was asked to comment, but was not involved with the work, characterized the consensus as a “helpful, concise reference guide for dermatologists.”

Dr. Lipner

The advantages of the study are the standardized methods used, “and the experience of the panel,” she said. “Study limitations include the response rate, which was less than 60%, and the risk of potential side effects are not stratified by age, sex, or comorbidities,” she added.

Dr. Fu disclosed that she is a consultant to Pfizer. Dr. Lipner reported having no relevant disclosures.

SAN DIEGO — Compared with the use of topical minoxidil for hair loss, the used of low-dose oral minoxidil (LDOM) can be considered when topical minoxidil is more expensive or logistically challenging, has plateaued in efficacy, leaves unwanted product residue, causes skin irritation, or exacerbates the inflammatory process.

Those are among the key recommendations that resulted from a modified eDelphi consensus of experts who convened to develop guidelines for LDOM prescribing and monitoring.

“Topical minoxidil is safe, effective, over-the-counter, and FDA-approved to treat the most common form of hair loss, androgenetic alopecia,” one of the study authors, Jennifer Fu, MD, a dermatologist who directs the Hair Disorders Clinic at the University of California, San Francisco, told this news organization following the annual meeting of the American Academy of Dermatology. The results of the expert consensus were presented during a poster session at the meeting. “It is often used off label for other types of hair loss, yet clinicians who treat hair loss know that patient compliance with topical minoxidil can be poor for a variety of reasons,” she said. “Patients report that it can be difficult to apply and complicate hair styling. For many patients, topical minoxidil can be drying or cause irritant or allergic contact reactions.”

Dr. Fu

LDOM has become a popular alternative for patients for whom topical minoxidil is logistically challenging, irritating, or ineffective, she continued. Although oral minoxidil is no longer a first-line antihypertensive agent given the risk of cardiovascular adverse effects at higher antihypertensive dosing (10-40 mg daily), a growing number of small studies have documented the use of LDOM at doses ranging from 0.25 mg to 5 mg daily as a safe, effective option for various types of hair loss.

“Given the current absence of larger trials on this topic, our research group identified a need for expert-based guidelines for prescribing and monitoring LDOM use in hair loss patients,” Dr. Fu said. “Our goal was to provide clinicians who treat hair loss patients a road map for using LDOM effectively, maximizing hair growth, and minimizing potential cardiovascular adverse effects.”


 

Arriving at a Consensus

The process involved 43 hair loss specialists from 12 countries with an average of 6.29 years of experience with LDOM for hair loss, who participated in a multi-round modified Delphi process. They considered questions that addressed LDOM safety, efficacy, dosing, and monitoring for hair loss, and consensus was reached if at least 70% of participants indicated “agree” or “strongly agree” on a five-point Likert scale. Round 1 consisted of 180 open-ended, multiple-choice, or Likert-scale questions, while round 2 involved 121 Likert-scale questions, round 3 consisted of 16 Likert-scale questions, and round 4 included 11 Likert-scale questions. In all, 94 items achieved Likert-scale consensus.

Specifically, experts on the panel found a direct benefit of LDOM for androgenetic alopecia, age-related patterned thinning, alopecia areata, telogen effluvium, traction alopecia, persistent chemotherapy-induced alopecia, and endocrine therapy-induced alopecia. They found a supportive benefit of LDOM for lichen planopilaris, frontal fibrosing alopecia, central centrifugal alopecia, and fibrosing alopecia in a patterned distribution.

“LDOM can be considered when topical minoxidil is more expensive, logistically challenging, has plateaued in efficacy, results in undesirable product residue/skin irritation,” or exacerbates inflammatory processes (ie eczema, psoriasis), they added.

Contraindications to LDOM listed in the consensus recommendations include hypersensitivity to minoxidil, significant drug-drug interactions with LDOM, a history of pericardial effusion/tamponade, pericarditis, heart failure, pulmonary hypertension associated with mitral stenosis, pheochromocytoma, and pregnancy/breastfeeding. Cited precautions of LDOM use include a history of tachycardia or arrhythmia, hypotension, renal impairment, and being on dialysis.

Dr. Fu and colleagues noted that the earliest time point at which LDOM should be expected to demonstrate efficacy is 3-6 months. “Baseline testing is not routine but may be considered in case of identified precautions,” they wrote. They also noted that LDOM can possibly be co-administered with beta-blockers with a specialty consultation, and with spironolactone in biologic female or transgender female patients with hirsutism, acne, polycystic ovary syndrome (PCOS), and with lower extremity and facial edema.

According to the consensus statement, the most frequently prescribed LDOM dosing regimen in adult females aged 18 years and older includes a starting dose of 1.25 mg daily, with a dosing range between 0.625 mg and 5 mg daily. For adult males, the most frequently prescribed dosing regimen is a starting dose of 2.5 daily, with a dosing range between 1.25 mg and 5 mg daily. The most frequently prescribed LDOM dosing regimen in adolescent females aged 12-17 years is a starting dose of 0.625 mg daily, with a dosing range of 0.625 to 2.5 mg daily. For adolescent males, the recommended regimen is a starting dose of 1.25 mg daily, with a dosing range of 1.25 mg to 5 mg daily.

“We hope that this consensus statement will guide our colleagues who would like to use LDOM to treat hair loss in their adult and adolescent patients,” Dr. Fu told this news organization. “These recommendations may be used to inform clinical practice until additional evidence-based data becomes available.”

She acknowledged certain limitations of the effort, including the fact that the expert panel was underrepresented in treating hair loss in pediatric patients, “and therefore failed to reach consensus on LDOM pediatric use and dosing,” she said. “We encourage our pediatric dermatology colleagues to further research LDOM in pediatric patients.”

In an interview, Shari Lipner, MD, PhD, associate professor of clinical dermatology, Weill Cornell Medicine, New York, who was asked to comment, but was not involved with the work, characterized the consensus as a “helpful, concise reference guide for dermatologists.”

Dr. Lipner

The advantages of the study are the standardized methods used, “and the experience of the panel,” she said. “Study limitations include the response rate, which was less than 60%, and the risk of potential side effects are not stratified by age, sex, or comorbidities,” she added.

Dr. Fu disclosed that she is a consultant to Pfizer. Dr. Lipner reported having no relevant disclosures.

FROM BMJ

The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.

Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.

Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.

Agata Lenczewska-Madsen, Regional Hospital Central Jutland

The Study

The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.

All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.

Among the findings:

• Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
• Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
• Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
• The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.

“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.

Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”

University of Texas Health Science Center at Houston

Dr. Wu

FROM BMJ

The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.

Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.

Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.

Agata Lenczewska-Madsen, Regional Hospital Central Jutland

The Study

The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.

All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.

Among the findings:

• Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
• Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
• Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
• The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.

“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.

Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”

University of Texas Health Science Center at Houston

Dr. Wu

FROM BMJ

The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.

Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.

Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.

Agata Lenczewska-Madsen, Regional Hospital Central Jutland

The Study

The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.

All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.

Among the findings:

• Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
• Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
• Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
• The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.

“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.

Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”

University of Texas Health Science Center at Houston

Dr. Wu

Here’s a new direction for smartphones in healthcare. 

Researchers from the National Institute of Standards and Technology (NIST), Boulder, Colorado, say a smartphone compass could be used to analyze biomarkers in body fluids — blood, sweat, urine, or saliva — to monitor or diagnose disease.

“We’re just at this point demonstrating this new way of sensing that we hope [will be] very accessible and very portable,” said Gary Zabow, PhD, a group leader in the applied physics division at NIST who supervised the research. 

In a proof-of-concept study, the researchers measured glucose levels in sangria, pinot grigio, and champagne. The detection limit reached micromolar concentrations — on par with or better than some widely used glucose sensors, such as continuous glucose monitors. They also accurately measured the pH levels of coffee, orange juice, and root beer.

More tests are needed to confirm the method works in biological fluids, so it could be a while before it’s available for clinical or commercial use. 

Still, the prospect is “exciting,” said Aydogan Ozcan, PhD, a bioengineering professor at the University of California, Los Angeles, who was not involved in the study. “It might enable new capabilities for advanced sensing applications in field settings or even at home.”

The advance builds on growing research using smartphones to put powerful medical devices in patients’ hands. A new AI-powered app can use a smartphone camera to detect skin cancer, while other apps administer cognitive tests to detect dementia. Smartphone cameras can even be harnessed for “advanced optical microscopes and sensors to the level where we could even see and detect individual DNA molecules with inexpensive optical attachments,” Dr. Ozcan said. More than six billion people worldwide own a smartphone.

The compass inside smartphones is a magnetometer — it measures magnetic fields. Normally it detects the earth’s magnetic fields, but it can also detect small, nearby magnets and changes in those magnets’ positions. 

The researchers embedded a small magnet inside a strip of “smart hydrogel — a piece of material that expands or contracts” when immersed in a solution, said Dr. Zabow.

As the hydrogel gets bigger or smaller, it moves the magnet, Dr. Zabow explained. For example, if the hydrogel is designed to expand when the solution is acidic or contract when it’s basic, it can move the magnet closer or farther from the phone’s magnetometer, providing an indicator of pH. For glucose, the hydrogel expands or contracts depending on the concentration of sugar in the liquid.

With some calibration and coding to translate that reading into a number, “you can effectively read out glucose or pH,” Dr. Zabow said.

Only a small strip of hydrogel is needed, “like a pH test strip that you use for a pool,” said first study author Mark Ferris, PhD, a postdoctoral researcher at NIST. 

Like a pool pH test strip, this test is meant to be “easy to use, and at that kind of price,” Dr. Ferris said. “It’s supposed to be something that’s cheap and disposable.” Each pH hydrogel strip is about 3 cents, and glucose strips are 16 cents, Dr. Ferris estimated. In bulk, those prices could go down.

Next the team plans to test the strips with biological fluids. But complex fluids like blood could pose a challenge, as other molecules present could react with the strip and affect the results. “It may be that you need to tweak the chemistry of the hydrogel to make sure it is really specific to one biomolecule and there is no interference from other biomolecules,” Dr. Zabow said.

The technique could be adapted to detect other biomarkers or molecules, the researchers said. It could also be used to check for chemical contaminants in tap, lake, or stream water. 
 

A version of this article appeared on Medscape.com.

Here’s a new direction for smartphones in healthcare. 

Researchers from the National Institute of Standards and Technology (NIST), Boulder, Colorado, say a smartphone compass could be used to analyze biomarkers in body fluids — blood, sweat, urine, or saliva — to monitor or diagnose disease.

“We’re just at this point demonstrating this new way of sensing that we hope [will be] very accessible and very portable,” said Gary Zabow, PhD, a group leader in the applied physics division at NIST who supervised the research. 

In a proof-of-concept study, the researchers measured glucose levels in sangria, pinot grigio, and champagne. The detection limit reached micromolar concentrations — on par with or better than some widely used glucose sensors, such as continuous glucose monitors. They also accurately measured the pH levels of coffee, orange juice, and root beer.

More tests are needed to confirm the method works in biological fluids, so it could be a while before it’s available for clinical or commercial use. 

Still, the prospect is “exciting,” said Aydogan Ozcan, PhD, a bioengineering professor at the University of California, Los Angeles, who was not involved in the study. “It might enable new capabilities for advanced sensing applications in field settings or even at home.”

The advance builds on growing research using smartphones to put powerful medical devices in patients’ hands. A new AI-powered app can use a smartphone camera to detect skin cancer, while other apps administer cognitive tests to detect dementia. Smartphone cameras can even be harnessed for “advanced optical microscopes and sensors to the level where we could even see and detect individual DNA molecules with inexpensive optical attachments,” Dr. Ozcan said. More than six billion people worldwide own a smartphone.

The compass inside smartphones is a magnetometer — it measures magnetic fields. Normally it detects the earth’s magnetic fields, but it can also detect small, nearby magnets and changes in those magnets’ positions. 

The researchers embedded a small magnet inside a strip of “smart hydrogel — a piece of material that expands or contracts” when immersed in a solution, said Dr. Zabow.

As the hydrogel gets bigger or smaller, it moves the magnet, Dr. Zabow explained. For example, if the hydrogel is designed to expand when the solution is acidic or contract when it’s basic, it can move the magnet closer or farther from the phone’s magnetometer, providing an indicator of pH. For glucose, the hydrogel expands or contracts depending on the concentration of sugar in the liquid.

With some calibration and coding to translate that reading into a number, “you can effectively read out glucose or pH,” Dr. Zabow said.

Only a small strip of hydrogel is needed, “like a pH test strip that you use for a pool,” said first study author Mark Ferris, PhD, a postdoctoral researcher at NIST. 

Like a pool pH test strip, this test is meant to be “easy to use, and at that kind of price,” Dr. Ferris said. “It’s supposed to be something that’s cheap and disposable.” Each pH hydrogel strip is about 3 cents, and glucose strips are 16 cents, Dr. Ferris estimated. In bulk, those prices could go down.

Next the team plans to test the strips with biological fluids. But complex fluids like blood could pose a challenge, as other molecules present could react with the strip and affect the results. “It may be that you need to tweak the chemistry of the hydrogel to make sure it is really specific to one biomolecule and there is no interference from other biomolecules,” Dr. Zabow said.

The technique could be adapted to detect other biomarkers or molecules, the researchers said. It could also be used to check for chemical contaminants in tap, lake, or stream water. 
 

A version of this article appeared on Medscape.com.

Here’s a new direction for smartphones in healthcare. 

Researchers from the National Institute of Standards and Technology (NIST), Boulder, Colorado, say a smartphone compass could be used to analyze biomarkers in body fluids — blood, sweat, urine, or saliva — to monitor or diagnose disease.

“We’re just at this point demonstrating this new way of sensing that we hope [will be] very accessible and very portable,” said Gary Zabow, PhD, a group leader in the applied physics division at NIST who supervised the research. 

In a proof-of-concept study, the researchers measured glucose levels in sangria, pinot grigio, and champagne. The detection limit reached micromolar concentrations — on par with or better than some widely used glucose sensors, such as continuous glucose monitors. They also accurately measured the pH levels of coffee, orange juice, and root beer.

More tests are needed to confirm the method works in biological fluids, so it could be a while before it’s available for clinical or commercial use. 

Still, the prospect is “exciting,” said Aydogan Ozcan, PhD, a bioengineering professor at the University of California, Los Angeles, who was not involved in the study. “It might enable new capabilities for advanced sensing applications in field settings or even at home.”

The advance builds on growing research using smartphones to put powerful medical devices in patients’ hands. A new AI-powered app can use a smartphone camera to detect skin cancer, while other apps administer cognitive tests to detect dementia. Smartphone cameras can even be harnessed for “advanced optical microscopes and sensors to the level where we could even see and detect individual DNA molecules with inexpensive optical attachments,” Dr. Ozcan said. More than six billion people worldwide own a smartphone.

The compass inside smartphones is a magnetometer — it measures magnetic fields. Normally it detects the earth’s magnetic fields, but it can also detect small, nearby magnets and changes in those magnets’ positions. 

The researchers embedded a small magnet inside a strip of “smart hydrogel — a piece of material that expands or contracts” when immersed in a solution, said Dr. Zabow.

As the hydrogel gets bigger or smaller, it moves the magnet, Dr. Zabow explained. For example, if the hydrogel is designed to expand when the solution is acidic or contract when it’s basic, it can move the magnet closer or farther from the phone’s magnetometer, providing an indicator of pH. For glucose, the hydrogel expands or contracts depending on the concentration of sugar in the liquid.

With some calibration and coding to translate that reading into a number, “you can effectively read out glucose or pH,” Dr. Zabow said.

Only a small strip of hydrogel is needed, “like a pH test strip that you use for a pool,” said first study author Mark Ferris, PhD, a postdoctoral researcher at NIST. 

Like a pool pH test strip, this test is meant to be “easy to use, and at that kind of price,” Dr. Ferris said. “It’s supposed to be something that’s cheap and disposable.” Each pH hydrogel strip is about 3 cents, and glucose strips are 16 cents, Dr. Ferris estimated. In bulk, those prices could go down.

Next the team plans to test the strips with biological fluids. But complex fluids like blood could pose a challenge, as other molecules present could react with the strip and affect the results. “It may be that you need to tweak the chemistry of the hydrogel to make sure it is really specific to one biomolecule and there is no interference from other biomolecules,” Dr. Zabow said.

The technique could be adapted to detect other biomarkers or molecules, the researchers said. It could also be used to check for chemical contaminants in tap, lake, or stream water. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the biosimilar ustekinumab-aekn (Selarsdi) for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis in adults and pediatric patients aged 6 years or older.

This is the second ustekinumab biosimilar approved by the regulatory agency and is the second biosimilar approval in the United States for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals. 

Ustekinumab (Stelara) is a human monoclonal antibody targeting interleukin (IL)–12 and IL-23. The drug, manufactured by Johnson & Johnson, totaled nearly $7 billion in sales in 2023 alone, according a press release. 

“Bringing Selarsdi to market in the US early next year presents a significant opportunity to improve patient access to a vital biologic in inflammatory disease and contribute to the reduction of inflationary pressure in healthcare costs,” the chairman and CEO of Alvotech said in the release. 

The first ustekinumab biosimilar, ustekinumab-auub (Wezlana), was approved by the FDA in on October 31, 2023 and is interchangeable with the reference product. This allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Besides psoriasis and psoriatic arthritis, ustekinumab-auub was also approved for treating moderate to severely active Crohn’s disease and ulcerative colitis. Ustekinumab-aekn does not have an interchangeability designation and was not approved for Crohn’s disease or ulcerative colitis. 

The approval of ustekinumab-aekn was based on two clinical studies. A randomized, double blind, multicenter, 52-week study of 581 patients with moderate to severe plaque psoriasis demonstrated that the biosimilar was as effective as the reference product, with equivalent safety and immunogenicity profiles. A phase 1, randomized, double-blind, single-dose, parallel-group, three-arm study also compared the pharmacokinetic profile of the biosimilar to ustekinumab in 294 healthy adults.

Ustekinumab-aekn is expected to be marketed in the United States on or after February 21, 2025 per a settlement and license agreement with Johnson & Johnson. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the biosimilar ustekinumab-aekn (Selarsdi) for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis in adults and pediatric patients aged 6 years or older.

This is the second ustekinumab biosimilar approved by the regulatory agency and is the second biosimilar approval in the United States for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals. 

Ustekinumab (Stelara) is a human monoclonal antibody targeting interleukin (IL)–12 and IL-23. The drug, manufactured by Johnson & Johnson, totaled nearly $7 billion in sales in 2023 alone, according a press release. 

“Bringing Selarsdi to market in the US early next year presents a significant opportunity to improve patient access to a vital biologic in inflammatory disease and contribute to the reduction of inflationary pressure in healthcare costs,” the chairman and CEO of Alvotech said in the release. 

The first ustekinumab biosimilar, ustekinumab-auub (Wezlana), was approved by the FDA in on October 31, 2023 and is interchangeable with the reference product. This allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Besides psoriasis and psoriatic arthritis, ustekinumab-auub was also approved for treating moderate to severely active Crohn’s disease and ulcerative colitis. Ustekinumab-aekn does not have an interchangeability designation and was not approved for Crohn’s disease or ulcerative colitis. 

The approval of ustekinumab-aekn was based on two clinical studies. A randomized, double blind, multicenter, 52-week study of 581 patients with moderate to severe plaque psoriasis demonstrated that the biosimilar was as effective as the reference product, with equivalent safety and immunogenicity profiles. A phase 1, randomized, double-blind, single-dose, parallel-group, three-arm study also compared the pharmacokinetic profile of the biosimilar to ustekinumab in 294 healthy adults.

Ustekinumab-aekn is expected to be marketed in the United States on or after February 21, 2025 per a settlement and license agreement with Johnson & Johnson. 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the biosimilar ustekinumab-aekn (Selarsdi) for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis in adults and pediatric patients aged 6 years or older.

This is the second ustekinumab biosimilar approved by the regulatory agency and is the second biosimilar approval in the United States for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals. 

Ustekinumab (Stelara) is a human monoclonal antibody targeting interleukin (IL)–12 and IL-23. The drug, manufactured by Johnson & Johnson, totaled nearly $7 billion in sales in 2023 alone, according a press release. 

“Bringing Selarsdi to market in the US early next year presents a significant opportunity to improve patient access to a vital biologic in inflammatory disease and contribute to the reduction of inflationary pressure in healthcare costs,” the chairman and CEO of Alvotech said in the release. 

The first ustekinumab biosimilar, ustekinumab-auub (Wezlana), was approved by the FDA in on October 31, 2023 and is interchangeable with the reference product. This allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Besides psoriasis and psoriatic arthritis, ustekinumab-auub was also approved for treating moderate to severely active Crohn’s disease and ulcerative colitis. Ustekinumab-aekn does not have an interchangeability designation and was not approved for Crohn’s disease or ulcerative colitis. 

The approval of ustekinumab-aekn was based on two clinical studies. A randomized, double blind, multicenter, 52-week study of 581 patients with moderate to severe plaque psoriasis demonstrated that the biosimilar was as effective as the reference product, with equivalent safety and immunogenicity profiles. A phase 1, randomized, double-blind, single-dose, parallel-group, three-arm study also compared the pharmacokinetic profile of the biosimilar to ustekinumab in 294 healthy adults.

Ustekinumab-aekn is expected to be marketed in the United States on or after February 21, 2025 per a settlement and license agreement with Johnson & Johnson. 

A version of this article appeared on Medscape.com.

The photo of the patient’s foot, sent from his campsite, included a cheeky note: “I remember you telling me that getting in trouble doing something was better than getting in trouble doing nothing. This lets me get out there and know that I have feedback.”

The “this” was the patient’s “foot selfie,” an approach that allows patients at a risk for diabetic foot ulcers (DFUs) to snap a picture and send it to their healthcare providers for evaluation.

This particular patient had an extensive history of previous wounds. Some had essentially kept him house-bound in the past, as he was afraid to get another one.

This time, however, he got an all-clear to keep on camping, “and we scheduled him in on the following Tuesday [for follow-up],” said the camper’s physician David G. Armstrong, DPM, MD, PhD, professor of surgery and neurological surgery, USC Keck School of Medicine, Los Angeles.

Dr. Armstrong is one of the researchers evaluating the concept of foot selfies. It’s a welcome advance, he and others said, and has been shown to help heal wounds and reverse pre-ulcer lesions. Research on foot selfies continues, but much more is needed to solve the issue of DFUs, diabetic foot infections (DFIs), and the high rates of reinfection, experts know.

Worldwide, about 18.6 million people have a DFU each year, including 1.6 million in the United States. About 50%-60% of ulcers become infected, with 20% of moderate to severe infections requiring amputation of the limb. The 5-year mortality rate for DFUs is 30%, but it climbs to 70% after amputation. While about 40% of ulcers heal within 12 weeks, 42% recur at the 1-year mark, setting up a vicious and costly cycle. Healthcare costs for patients with diabetes and DFUs are five times as high as costs for patients with diabetes but no DFUs. The per capita cost to treat a DFU in America is $17,500.

While the statistics paint a grim picture, progress is being made on several fronts:

• US Food and Drug Administration (FDA) guidance on the development of drugs for DFUs, under evaluation, is forthcoming.
• New treatments are under study.
• A multidisciplinary team approach is known to improve outcomes.

Anatomy of a DFU

When neuropathy develops in those with diabetes, they no longer have what Dr. Armstrong calls the “gift” of pain perception. “They can wear a hole in their foot like you and I wear a hole in our sock or shoe,” he said. “That hole is called a diabetic foot ulcer.”

A DFU is an open wound on the foot, often occurring when bleeding develops beneath a callus and then the callus wears away. Deeper tissues of the foot are then exposed.

About half of the DFUs get infected, hence the FDA guidance, said Dr. Armstrong, who is also founding president of the American Limb Preservation Society, which aims to eliminate preventable amputations within the next generation. Every 20 seconds, Dr. Armstrong said, someone in the world loses a leg due to diabetes.
 

FDA Guidance on Drug Development for DFIs

In October, the FDA issued draft guidance for industry to articulate the design of clinical trials for developing antibacterial drugs to treat DFIs without concomitant bone and joint involvement. Comments closed on December 18. Among the points in the guidance, which is nonbinding, are to include DFIs of varying depths and extent in phase 3 trials and ideally to include only those patients who have not had prior antibacterial treatment for the current DFI.

According to an FDA spokesperson, “The agency is working to finalize the guidance. However, a timeline for its release has not yet been established.”

The good news about the upcoming FDA guidance, Dr. Armstrong said, is that the agency has realized the importance of treating the infections. Fully one third of direct costs of care for diabetes are spent on the lower extremities, he said. Keeping patients out of the hospital, uninfected, and “keeping legs on bodies” are all important goals, he said.

Pharmaceutical firms need to understand that “you aren’t dealing with a normal ulcer,” said Andrew J.M. Boulton, MD, professor of medicine at the University of Manchester and physician consultant at the Manchester Royal Infirmary, Manchester, England, and a visiting professor at the University of Miami. For research, “the most important thing is to take account of off-loading the ulcers,” he said. “Most ulcers will heal if put in a boot.”

Dr. Boulton, like Dr. Armstrong, a long-time expert in the field, contended that pharma has not understood this concept and has wasted millions over the last three decades doing studies that were poorly designed and controlled.
 

Treatments: Current, Under Study

Currently, DFIs are treated with antimicrobial therapy, without or without debridement, along with a clinical assessment for ischemia. If ischemia is found, care progresses to wound care and off-loading devices, such as healing sandals. Clinicians then assess the likelihood of improved outcomes with revascularization based on operative risks and distribution of lower extremity artery disease and proceed depending on the likelihood. If osteomyelitis testing shows it is present, providers proceed to wound debridement, limb-sparing amputation, and prolonged antimicrobials, as needed.

More options are needed, Dr. Armstrong said.

Among the many approaches under study:

• DFUs can be accurately detected by applying artificial intelligence to the “foot selfie” images taken by patients on smartphones, research by Dr.  and  has found.
• After a phase 3 study of  for DFUs originally intending to enroll 300 subjects was discontinued because of slow patient recruitment, an interim analysis was conducted on 44 participants. It showed a positive trend toward wound closure in the group receiving the injected gene therapy, VM202 (ENGENSIS), in their calf muscles. VM202 is a plasmid DNA-encoding human hepatocyte growth factor. While those in both the intervention and placebo groups showed wound-closing effects at month 6, in 23 patients with neuro-ischemic ulcers, the percentage of those reaching complete closure of the DFU was significantly higher in the treated group at months 3, 4, and 5 (P = .0391, .0391, and .0361, respectively). After excluding two outliers, the difference in months 3-6 became more significant (P = .03).
• An closed more DFUs than standard care after 12 weeks — 70% vs 34% (P = .00032). Of the 100 participants randomized, 50 per group, 42% of the treatment group and 56% of the control group experienced adverse events, with eight withdrawn due to serious adverse events (such as osteomyelitis).
• A closed more refractory DFUs over a 16-week study than standard sharp debridement, with 65% of water-treated ulcers healed but just 42% of the standard care group (P = .021, unadjusted).
• Researchers from UC Davis and VA Northern California Healthcare are evaluating timolol, a beta adrenergic receptor blocker already approved for topical administration for glaucoma, as a way to heal chronic DFUs faster. After demonstrating that the medication worked in animal models, researchers then launched a study to use it off-label for DFUs. While data are still being analyzed, researcher Roslyn (Rivkah) Isseroff, MD, of UC Davis and VA, said that data so far demonstrate that the timolol reduced transepidermal water loss in the healed wounds, and that is linked with a decrease in re-ulceration.

The Power of a Team

Multidisciplinary approaches to treatment are effective in reducing amputation, with one review of 33 studies finding the approach worked to decrease amputation in 94% of them. “The American Limb Preservation Society (ALPS) lists 30 programs,” said Dr. Armstrong, the founding president of the organization. “There may be as many as 100.”

Team compositions vary but usually include at least one medical specialty clinician, such as infectious disease, primary care, or endocrinology, and two or more specialty clinicians, such as vascular, podiatric, orthopedic, or plastic surgery. A shoe specialist is needed to prescribe and manage footwear. Other important team members include nutrition experts and behavioral health professionals to deal with associated depression.

Johns Hopkins’ Multidisciplinary Diabetic Foot and Wound Service launched in 2012 and includes vascular surgeons, surgical podiatrists, endocrinologists, wound care nurses, advanced practice staff, board-certified wound care specialists, orthopedic surgeons, infection disease experts, physical therapists, and certified orthotists.

“This interdisciplinary care model has been repeatedly validated by research as superior for limb salvage and wound healing,” said Nestoras Mathioudakis, MD, codirector of the service. “For instance, endocrinologists and diabetes educators are crucial for managing uncontrolled diabetes — a key factor in infection and delayed wound healing. Similarly, vascular surgeons play a vital role in addressing peripheral arterial disease to improve blood flow to the affected area.”

“Diabetic foot ulcers might require prolonged periods of specialized care, including meticulous wound management and off-loading, overseen by surgical podiatrists and wound care experts,” he said. “In cases where infection is present, particularly with multidrug resistant organisms or when standard antibiotics are contraindicated, the insight of an infectious disease specialist is invaluable.”

While the makeup of teams varies from location to location, he said “the hallmark of effective teams is their ability to comprehensively manage glycemic control, foot wounds, vascular disease, and infections.”

The power of teams, Dr. Armstrong said, is very much evident after his weekly “foot selfie rounds” conducted Mondays at 7 AM, with an “all feet on deck” approach. “Not a week goes by when we don’t stop a hospitalization,” he said of the team evaluating the photos, due to detecting issues early, while still in the manageable state.

Teams can trump technology, Dr. Armstrong said. A team of just a primary care doctor and a podiatrist can make a significant reduction in amputations, he said, just by a “Knock your socks off” approach. He reminds primary care doctors that observing the feet of their patients with diabetes can go a long way to reducing DFUs and the hospitalizations and amputations that can result.

Dr. Mathioudakis and Dr. Isseroff reported no disclosures. Dr. Boulton consults for Urgo Medical, Nevro Corporation, and AOT, Inc. Dr. Armstrong reported receiving consulting fees from Podimetrics; Molnlycke; Cardiovascular Systems, Inc.; Endo Pharmaceuticals; and Averitas Pharma (GRT US).

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

The photo of the patient’s foot, sent from his campsite, included a cheeky note: “I remember you telling me that getting in trouble doing something was better than getting in trouble doing nothing. This lets me get out there and know that I have feedback.”

The “this” was the patient’s “foot selfie,” an approach that allows patients at a risk for diabetic foot ulcers (DFUs) to snap a picture and send it to their healthcare providers for evaluation.

This particular patient had an extensive history of previous wounds. Some had essentially kept him house-bound in the past, as he was afraid to get another one.

This time, however, he got an all-clear to keep on camping, “and we scheduled him in on the following Tuesday [for follow-up],” said the camper’s physician David G. Armstrong, DPM, MD, PhD, professor of surgery and neurological surgery, USC Keck School of Medicine, Los Angeles.

Dr. Armstrong is one of the researchers evaluating the concept of foot selfies. It’s a welcome advance, he and others said, and has been shown to help heal wounds and reverse pre-ulcer lesions. Research on foot selfies continues, but much more is needed to solve the issue of DFUs, diabetic foot infections (DFIs), and the high rates of reinfection, experts know.

Worldwide, about 18.6 million people have a DFU each year, including 1.6 million in the United States. About 50%-60% of ulcers become infected, with 20% of moderate to severe infections requiring amputation of the limb. The 5-year mortality rate for DFUs is 30%, but it climbs to 70% after amputation. While about 40% of ulcers heal within 12 weeks, 42% recur at the 1-year mark, setting up a vicious and costly cycle. Healthcare costs for patients with diabetes and DFUs are five times as high as costs for patients with diabetes but no DFUs. The per capita cost to treat a DFU in America is $17,500.

While the statistics paint a grim picture, progress is being made on several fronts:

• US Food and Drug Administration (FDA) guidance on the development of drugs for DFUs, under evaluation, is forthcoming.
• New treatments are under study.
• A multidisciplinary team approach is known to improve outcomes.

Anatomy of a DFU

When neuropathy develops in those with diabetes, they no longer have what Dr. Armstrong calls the “gift” of pain perception. “They can wear a hole in their foot like you and I wear a hole in our sock or shoe,” he said. “That hole is called a diabetic foot ulcer.”

A DFU is an open wound on the foot, often occurring when bleeding develops beneath a callus and then the callus wears away. Deeper tissues of the foot are then exposed.

About half of the DFUs get infected, hence the FDA guidance, said Dr. Armstrong, who is also founding president of the American Limb Preservation Society, which aims to eliminate preventable amputations within the next generation. Every 20 seconds, Dr. Armstrong said, someone in the world loses a leg due to diabetes.
 

FDA Guidance on Drug Development for DFIs

In October, the FDA issued draft guidance for industry to articulate the design of clinical trials for developing antibacterial drugs to treat DFIs without concomitant bone and joint involvement. Comments closed on December 18. Among the points in the guidance, which is nonbinding, are to include DFIs of varying depths and extent in phase 3 trials and ideally to include only those patients who have not had prior antibacterial treatment for the current DFI.

According to an FDA spokesperson, “The agency is working to finalize the guidance. However, a timeline for its release has not yet been established.”

The good news about the upcoming FDA guidance, Dr. Armstrong said, is that the agency has realized the importance of treating the infections. Fully one third of direct costs of care for diabetes are spent on the lower extremities, he said. Keeping patients out of the hospital, uninfected, and “keeping legs on bodies” are all important goals, he said.

Pharmaceutical firms need to understand that “you aren’t dealing with a normal ulcer,” said Andrew J.M. Boulton, MD, professor of medicine at the University of Manchester and physician consultant at the Manchester Royal Infirmary, Manchester, England, and a visiting professor at the University of Miami. For research, “the most important thing is to take account of off-loading the ulcers,” he said. “Most ulcers will heal if put in a boot.”

Dr. Boulton, like Dr. Armstrong, a long-time expert in the field, contended that pharma has not understood this concept and has wasted millions over the last three decades doing studies that were poorly designed and controlled.
 

Treatments: Current, Under Study

Currently, DFIs are treated with antimicrobial therapy, without or without debridement, along with a clinical assessment for ischemia. If ischemia is found, care progresses to wound care and off-loading devices, such as healing sandals. Clinicians then assess the likelihood of improved outcomes with revascularization based on operative risks and distribution of lower extremity artery disease and proceed depending on the likelihood. If osteomyelitis testing shows it is present, providers proceed to wound debridement, limb-sparing amputation, and prolonged antimicrobials, as needed.

More options are needed, Dr. Armstrong said.

Among the many approaches under study:

• DFUs can be accurately detected by applying artificial intelligence to the “foot selfie” images taken by patients on smartphones, research by Dr.  and  has found.
• After a phase 3 study of  for DFUs originally intending to enroll 300 subjects was discontinued because of slow patient recruitment, an interim analysis was conducted on 44 participants. It showed a positive trend toward wound closure in the group receiving the injected gene therapy, VM202 (ENGENSIS), in their calf muscles. VM202 is a plasmid DNA-encoding human hepatocyte growth factor. While those in both the intervention and placebo groups showed wound-closing effects at month 6, in 23 patients with neuro-ischemic ulcers, the percentage of those reaching complete closure of the DFU was significantly higher in the treated group at months 3, 4, and 5 (P = .0391, .0391, and .0361, respectively). After excluding two outliers, the difference in months 3-6 became more significant (P = .03).
• An closed more DFUs than standard care after 12 weeks — 70% vs 34% (P = .00032). Of the 100 participants randomized, 50 per group, 42% of the treatment group and 56% of the control group experienced adverse events, with eight withdrawn due to serious adverse events (such as osteomyelitis).
• A closed more refractory DFUs over a 16-week study than standard sharp debridement, with 65% of water-treated ulcers healed but just 42% of the standard care group (P = .021, unadjusted).
• Researchers from UC Davis and VA Northern California Healthcare are evaluating timolol, a beta adrenergic receptor blocker already approved for topical administration for glaucoma, as a way to heal chronic DFUs faster. After demonstrating that the medication worked in animal models, researchers then launched a study to use it off-label for DFUs. While data are still being analyzed, researcher Roslyn (Rivkah) Isseroff, MD, of UC Davis and VA, said that data so far demonstrate that the timolol reduced transepidermal water loss in the healed wounds, and that is linked with a decrease in re-ulceration.

The Power of a Team

Multidisciplinary approaches to treatment are effective in reducing amputation, with one review of 33 studies finding the approach worked to decrease amputation in 94% of them. “The American Limb Preservation Society (ALPS) lists 30 programs,” said Dr. Armstrong, the founding president of the organization. “There may be as many as 100.”

Team compositions vary but usually include at least one medical specialty clinician, such as infectious disease, primary care, or endocrinology, and two or more specialty clinicians, such as vascular, podiatric, orthopedic, or plastic surgery. A shoe specialist is needed to prescribe and manage footwear. Other important team members include nutrition experts and behavioral health professionals to deal with associated depression.

Johns Hopkins’ Multidisciplinary Diabetic Foot and Wound Service launched in 2012 and includes vascular surgeons, surgical podiatrists, endocrinologists, wound care nurses, advanced practice staff, board-certified wound care specialists, orthopedic surgeons, infection disease experts, physical therapists, and certified orthotists.

“This interdisciplinary care model has been repeatedly validated by research as superior for limb salvage and wound healing,” said Nestoras Mathioudakis, MD, codirector of the service. “For instance, endocrinologists and diabetes educators are crucial for managing uncontrolled diabetes — a key factor in infection and delayed wound healing. Similarly, vascular surgeons play a vital role in addressing peripheral arterial disease to improve blood flow to the affected area.”

“Diabetic foot ulcers might require prolonged periods of specialized care, including meticulous wound management and off-loading, overseen by surgical podiatrists and wound care experts,” he said. “In cases where infection is present, particularly with multidrug resistant organisms or when standard antibiotics are contraindicated, the insight of an infectious disease specialist is invaluable.”

While the makeup of teams varies from location to location, he said “the hallmark of effective teams is their ability to comprehensively manage glycemic control, foot wounds, vascular disease, and infections.”

The power of teams, Dr. Armstrong said, is very much evident after his weekly “foot selfie rounds” conducted Mondays at 7 AM, with an “all feet on deck” approach. “Not a week goes by when we don’t stop a hospitalization,” he said of the team evaluating the photos, due to detecting issues early, while still in the manageable state.

Teams can trump technology, Dr. Armstrong said. A team of just a primary care doctor and a podiatrist can make a significant reduction in amputations, he said, just by a “Knock your socks off” approach. He reminds primary care doctors that observing the feet of their patients with diabetes can go a long way to reducing DFUs and the hospitalizations and amputations that can result.

Dr. Mathioudakis and Dr. Isseroff reported no disclosures. Dr. Boulton consults for Urgo Medical, Nevro Corporation, and AOT, Inc. Dr. Armstrong reported receiving consulting fees from Podimetrics; Molnlycke; Cardiovascular Systems, Inc.; Endo Pharmaceuticals; and Averitas Pharma (GRT US).

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

The photo of the patient’s foot, sent from his campsite, included a cheeky note: “I remember you telling me that getting in trouble doing something was better than getting in trouble doing nothing. This lets me get out there and know that I have feedback.”

The “this” was the patient’s “foot selfie,” an approach that allows patients at a risk for diabetic foot ulcers (DFUs) to snap a picture and send it to their healthcare providers for evaluation.

This particular patient had an extensive history of previous wounds. Some had essentially kept him house-bound in the past, as he was afraid to get another one.

This time, however, he got an all-clear to keep on camping, “and we scheduled him in on the following Tuesday [for follow-up],” said the camper’s physician David G. Armstrong, DPM, MD, PhD, professor of surgery and neurological surgery, USC Keck School of Medicine, Los Angeles.

Dr. Armstrong is one of the researchers evaluating the concept of foot selfies. It’s a welcome advance, he and others said, and has been shown to help heal wounds and reverse pre-ulcer lesions. Research on foot selfies continues, but much more is needed to solve the issue of DFUs, diabetic foot infections (DFIs), and the high rates of reinfection, experts know.

Worldwide, about 18.6 million people have a DFU each year, including 1.6 million in the United States. About 50%-60% of ulcers become infected, with 20% of moderate to severe infections requiring amputation of the limb. The 5-year mortality rate for DFUs is 30%, but it climbs to 70% after amputation. While about 40% of ulcers heal within 12 weeks, 42% recur at the 1-year mark, setting up a vicious and costly cycle. Healthcare costs for patients with diabetes and DFUs are five times as high as costs for patients with diabetes but no DFUs. The per capita cost to treat a DFU in America is $17,500.

While the statistics paint a grim picture, progress is being made on several fronts:

• US Food and Drug Administration (FDA) guidance on the development of drugs for DFUs, under evaluation, is forthcoming.
• New treatments are under study.
• A multidisciplinary team approach is known to improve outcomes.

Anatomy of a DFU

When neuropathy develops in those with diabetes, they no longer have what Dr. Armstrong calls the “gift” of pain perception. “They can wear a hole in their foot like you and I wear a hole in our sock or shoe,” he said. “That hole is called a diabetic foot ulcer.”

A DFU is an open wound on the foot, often occurring when bleeding develops beneath a callus and then the callus wears away. Deeper tissues of the foot are then exposed.

About half of the DFUs get infected, hence the FDA guidance, said Dr. Armstrong, who is also founding president of the American Limb Preservation Society, which aims to eliminate preventable amputations within the next generation. Every 20 seconds, Dr. Armstrong said, someone in the world loses a leg due to diabetes.
 

FDA Guidance on Drug Development for DFIs

In October, the FDA issued draft guidance for industry to articulate the design of clinical trials for developing antibacterial drugs to treat DFIs without concomitant bone and joint involvement. Comments closed on December 18. Among the points in the guidance, which is nonbinding, are to include DFIs of varying depths and extent in phase 3 trials and ideally to include only those patients who have not had prior antibacterial treatment for the current DFI.

According to an FDA spokesperson, “The agency is working to finalize the guidance. However, a timeline for its release has not yet been established.”

The good news about the upcoming FDA guidance, Dr. Armstrong said, is that the agency has realized the importance of treating the infections. Fully one third of direct costs of care for diabetes are spent on the lower extremities, he said. Keeping patients out of the hospital, uninfected, and “keeping legs on bodies” are all important goals, he said.

Pharmaceutical firms need to understand that “you aren’t dealing with a normal ulcer,” said Andrew J.M. Boulton, MD, professor of medicine at the University of Manchester and physician consultant at the Manchester Royal Infirmary, Manchester, England, and a visiting professor at the University of Miami. For research, “the most important thing is to take account of off-loading the ulcers,” he said. “Most ulcers will heal if put in a boot.”

Dr. Boulton, like Dr. Armstrong, a long-time expert in the field, contended that pharma has not understood this concept and has wasted millions over the last three decades doing studies that were poorly designed and controlled.
 

Treatments: Current, Under Study

Currently, DFIs are treated with antimicrobial therapy, without or without debridement, along with a clinical assessment for ischemia. If ischemia is found, care progresses to wound care and off-loading devices, such as healing sandals. Clinicians then assess the likelihood of improved outcomes with revascularization based on operative risks and distribution of lower extremity artery disease and proceed depending on the likelihood. If osteomyelitis testing shows it is present, providers proceed to wound debridement, limb-sparing amputation, and prolonged antimicrobials, as needed.

More options are needed, Dr. Armstrong said.

Among the many approaches under study:

• DFUs can be accurately detected by applying artificial intelligence to the “foot selfie” images taken by patients on smartphones, research by Dr.  and  has found.
• After a phase 3 study of  for DFUs originally intending to enroll 300 subjects was discontinued because of slow patient recruitment, an interim analysis was conducted on 44 participants. It showed a positive trend toward wound closure in the group receiving the injected gene therapy, VM202 (ENGENSIS), in their calf muscles. VM202 is a plasmid DNA-encoding human hepatocyte growth factor. While those in both the intervention and placebo groups showed wound-closing effects at month 6, in 23 patients with neuro-ischemic ulcers, the percentage of those reaching complete closure of the DFU was significantly higher in the treated group at months 3, 4, and 5 (P = .0391, .0391, and .0361, respectively). After excluding two outliers, the difference in months 3-6 became more significant (P = .03).
• An closed more DFUs than standard care after 12 weeks — 70% vs 34% (P = .00032). Of the 100 participants randomized, 50 per group, 42% of the treatment group and 56% of the control group experienced adverse events, with eight withdrawn due to serious adverse events (such as osteomyelitis).
• A closed more refractory DFUs over a 16-week study than standard sharp debridement, with 65% of water-treated ulcers healed but just 42% of the standard care group (P = .021, unadjusted).
• Researchers from UC Davis and VA Northern California Healthcare are evaluating timolol, a beta adrenergic receptor blocker already approved for topical administration for glaucoma, as a way to heal chronic DFUs faster. After demonstrating that the medication worked in animal models, researchers then launched a study to use it off-label for DFUs. While data are still being analyzed, researcher Roslyn (Rivkah) Isseroff, MD, of UC Davis and VA, said that data so far demonstrate that the timolol reduced transepidermal water loss in the healed wounds, and that is linked with a decrease in re-ulceration.

The Power of a Team

Multidisciplinary approaches to treatment are effective in reducing amputation, with one review of 33 studies finding the approach worked to decrease amputation in 94% of them. “The American Limb Preservation Society (ALPS) lists 30 programs,” said Dr. Armstrong, the founding president of the organization. “There may be as many as 100.”

Team compositions vary but usually include at least one medical specialty clinician, such as infectious disease, primary care, or endocrinology, and two or more specialty clinicians, such as vascular, podiatric, orthopedic, or plastic surgery. A shoe specialist is needed to prescribe and manage footwear. Other important team members include nutrition experts and behavioral health professionals to deal with associated depression.

Johns Hopkins’ Multidisciplinary Diabetic Foot and Wound Service launched in 2012 and includes vascular surgeons, surgical podiatrists, endocrinologists, wound care nurses, advanced practice staff, board-certified wound care specialists, orthopedic surgeons, infection disease experts, physical therapists, and certified orthotists.

“This interdisciplinary care model has been repeatedly validated by research as superior for limb salvage and wound healing,” said Nestoras Mathioudakis, MD, codirector of the service. “For instance, endocrinologists and diabetes educators are crucial for managing uncontrolled diabetes — a key factor in infection and delayed wound healing. Similarly, vascular surgeons play a vital role in addressing peripheral arterial disease to improve blood flow to the affected area.”

“Diabetic foot ulcers might require prolonged periods of specialized care, including meticulous wound management and off-loading, overseen by surgical podiatrists and wound care experts,” he said. “In cases where infection is present, particularly with multidrug resistant organisms or when standard antibiotics are contraindicated, the insight of an infectious disease specialist is invaluable.”

While the makeup of teams varies from location to location, he said “the hallmark of effective teams is their ability to comprehensively manage glycemic control, foot wounds, vascular disease, and infections.”

The power of teams, Dr. Armstrong said, is very much evident after his weekly “foot selfie rounds” conducted Mondays at 7 AM, with an “all feet on deck” approach. “Not a week goes by when we don’t stop a hospitalization,” he said of the team evaluating the photos, due to detecting issues early, while still in the manageable state.

Teams can trump technology, Dr. Armstrong said. A team of just a primary care doctor and a podiatrist can make a significant reduction in amputations, he said, just by a “Knock your socks off” approach. He reminds primary care doctors that observing the feet of their patients with diabetes can go a long way to reducing DFUs and the hospitalizations and amputations that can result.

Dr. Mathioudakis and Dr. Isseroff reported no disclosures. Dr. Boulton consults for Urgo Medical, Nevro Corporation, and AOT, Inc. Dr. Armstrong reported receiving consulting fees from Podimetrics; Molnlycke; Cardiovascular Systems, Inc.; Endo Pharmaceuticals; and Averitas Pharma (GRT US).

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