Dermatology News

The Food and Drug Administration (FDA) has approved spesolimab-sbzo, an interleukin (IL)-36 receptor antagonist, for the treatment of generalized pustular psoriasis (GPP) in adults and in pediatric patients aged ≥ 12 years who weigh ≥ 40 kg, according to an announcement from the manufacturer. 

This is an expanded indication for spesolimab-sbzo, first approved in September 2022 for treating GPP flares. Developed by Boehringer Ingelheim and marketed under the name Spevigo, the product is an injectable antibody that blocks the IL-36 receptor, a key part of the pathway shown to be involved in the cause of GPP, which is rare and is a potentially-life-threatening disease.

According to a press release from the company, the FDA’s approval of the expanded indication was based on the results of a 48-week clinical trial of 123 patients (Effisayil 2), which showed that individuals who received spesolimab experienced a significant 84% reduction in GPP flares compared with those who received placebo. Among 30 study participants who received a high treatment dose, no flares were observed after week 4. Among all patients who received spesolimab-sbzo, treatment was associated with an increased incidence (defined as ≥ 9 cases per 100 patient-years) of injection site reactions, urinary tract infections, arthralgia, and pruritus compared with placebo. 

Spesolimab-sbzo is currently available in 48 countries, according to the Boehringer Ingelheim release, which states that the approval makes it the first targeted therapy that is available for the acute and chronic treatment of patients with GPP.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved spesolimab-sbzo, an interleukin (IL)-36 receptor antagonist, for the treatment of generalized pustular psoriasis (GPP) in adults and in pediatric patients aged ≥ 12 years who weigh ≥ 40 kg, according to an announcement from the manufacturer. 

This is an expanded indication for spesolimab-sbzo, first approved in September 2022 for treating GPP flares. Developed by Boehringer Ingelheim and marketed under the name Spevigo, the product is an injectable antibody that blocks the IL-36 receptor, a key part of the pathway shown to be involved in the cause of GPP, which is rare and is a potentially-life-threatening disease.

According to a press release from the company, the FDA’s approval of the expanded indication was based on the results of a 48-week clinical trial of 123 patients (Effisayil 2), which showed that individuals who received spesolimab experienced a significant 84% reduction in GPP flares compared with those who received placebo. Among 30 study participants who received a high treatment dose, no flares were observed after week 4. Among all patients who received spesolimab-sbzo, treatment was associated with an increased incidence (defined as ≥ 9 cases per 100 patient-years) of injection site reactions, urinary tract infections, arthralgia, and pruritus compared with placebo. 

Spesolimab-sbzo is currently available in 48 countries, according to the Boehringer Ingelheim release, which states that the approval makes it the first targeted therapy that is available for the acute and chronic treatment of patients with GPP.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved spesolimab-sbzo, an interleukin (IL)-36 receptor antagonist, for the treatment of generalized pustular psoriasis (GPP) in adults and in pediatric patients aged ≥ 12 years who weigh ≥ 40 kg, according to an announcement from the manufacturer. 

This is an expanded indication for spesolimab-sbzo, first approved in September 2022 for treating GPP flares. Developed by Boehringer Ingelheim and marketed under the name Spevigo, the product is an injectable antibody that blocks the IL-36 receptor, a key part of the pathway shown to be involved in the cause of GPP, which is rare and is a potentially-life-threatening disease.

According to a press release from the company, the FDA’s approval of the expanded indication was based on the results of a 48-week clinical trial of 123 patients (Effisayil 2), which showed that individuals who received spesolimab experienced a significant 84% reduction in GPP flares compared with those who received placebo. Among 30 study participants who received a high treatment dose, no flares were observed after week 4. Among all patients who received spesolimab-sbzo, treatment was associated with an increased incidence (defined as ≥ 9 cases per 100 patient-years) of injection site reactions, urinary tract infections, arthralgia, and pruritus compared with placebo. 

Spesolimab-sbzo is currently available in 48 countries, according to the Boehringer Ingelheim release, which states that the approval makes it the first targeted therapy that is available for the acute and chronic treatment of patients with GPP.

A version of this article appeared on Medscape.com.

SAN DIEGO — Among patients with skin of color and moderate to severe atopic dermatitis (AD) who underwent 16 weeks of treatment with lebrikizumab, 68% achieved a 75% reduction in the Eczema Area and Severity Index (EASI-75), interim results from a novel phase 3b trial showed.

Lebrikizumab, a novel monoclonal antibody being developed by Eli Lilly and Co, binds with high affinity to interleukin (IL)–13, thereby blocking the downstream effects of IL-13 with high potency, one of the study investigators, Jill S. Waibel, MD, a dermatologist in Miami, said at the annual meeting of the American Academy of Dermatology. Though the efficacy and safety of lebrikizumab to treat moderate to severe AD have been established in phase 3 studies, including subset analyses by race and ethnicity, “there is a paucity of data to guide the treatment of moderate-to-severe AD in populations traditionally under-represented in clinical trials, including patients with skin of color,” she said.

During a late-breaking abstract session, Dr. Waibel presented interim 16-week results from ADmirable, a phase 3b, open-label, 24-week study, was the first study to evaluate the safety and efficacy of lebrikizumab in adult and adolescents with skin of color and moderate to severe AD. At baseline and at 2 weeks, patients received a 500-mg loading dose of lebrikizumab. Through week 16, they received a 250-mg dose every 2 weeks. The study’s primary endpoint was the proportion of patients who achieved a 75% reduction in EASI-75 at week 16. “If they achieved the primary endpoint at week 16, they went to a 250-mg dose every 4 weeks,” Dr. Waibel said. “If they did not achieve that [primary endpoint] they stayed on the 250-mg dose every 2 weeks.”

The analysis included 50 patients with skin types IV, V, and VI who self-reported their race as Black or African American, American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander. They had chronic AD for at least 1 year, moderate to severe disease at baseline, a history of an inadequate response to topical medications, and were naive to biologics indicated for the treatment of AD.

Week 16 outcomes of interest were the EASI, the Investigator’s Global Assessment (IGA) of 0 or 1, the Pruritus Numerical Rating Scale (NRS), and PDCA-Derm, a scale developed by Eli Lilly and Co that was used to compare postinflammatory lesions to unaffected adjacent normal skin. All data for statistical analyses were summarized as observed.

At baseline, the mean age of the 50 patients was 42 years, 46% were women, their mean body mass index was 30.2, and the mean age at AD onset was 23 years. Most study participants (80%) were Black or African American, 14% were Asian, and 6% were American Indian or Alaska Native; 78% were not Hispanic or Latino and 22% were Hispanic or Latino. The mean EASI score was 28.1, the mean body surface area affected was 41.7%, and the mean Pruritus NRS score was 7.2 out of 11. According to the PDCA-Derm scale, 18% of patients had hypopigmented lesions, and 54% had hyperpigmented lesions.

After 16 weeks of treatment, 68% of patients achieved an EASI-75 response, whereas 46% achieved an EASI-90 response, Dr. Waibel reported at the meeting. In addition, 39% of patients achieved an IGA score of 0 or 1, 56% achieved a ≥ 4-point improvement on the Pruritus NRS, and 66% achieved a ≥ 3-point improvement on the Pruritus NRS. The PDCA-Derm score identified improvement in postinflammatory hyperpigmented lesions in 12 of 21 patients and improvement to normal skin tone in six of 21 patients.

“I have a large population [with skin of color in my practice],” Dr. Waibel said. “I usually tell my [patients with postinflammatory hyperpigmentation] that it takes 6 months to see improvement. In this study, we saw patients achieve improvement in skin tone in a 4-month time frame. PIH is sometimes more distressing than a primary condition, whether it’s acne or atopic dermatitis. In this case, it was surprisingly improved with lebrikizumab.”

No new safety signals or serious adverse events were observed. “This is very exciting because it’s the first time there has been a trial focusing on [patients with skin of color] with moderate to severe eczema in skin types IV-VI,” Dr. Waibel said.

In an interview, the study’s lead investigator, Andrew Alexis, MD, MPH, vice chair for diversity and inclusion in the department of dermatology and professor of clinical dermatology at Weill Cornell Medicine, New York City, said that the interim results from this study “ add valuable, clinically relevant data on the treatment of moderate to severe AD in patient populations with skin of color.”

“An interesting finding,” he continued, “was that improvement in postinflammatory hyperpigmented lesions was seen in 12 of 21 patients and improvement to normal skin tone was observed in six of 21 patients at week 16. This is particularly relevant to patients with skin of color who frequently suffer from pigmentary changes in association with their AD.”

Lebrikizumab was approved in November 2023 in Europe for the treatment of moderate to severe AD in people aged 12 years or older and is currently under review by the Food and Drug Administration for treatment of AD. 

Both Dr. Waibel and Dr. Alexis disclosed numerous conflicts of interest from various pharmaceutical companies, including serving as a consultant and/or advisor to Eli Lilly and Co.
 

A version of this article appeared on Medscape.com.
 

SAN DIEGO — Among patients with skin of color and moderate to severe atopic dermatitis (AD) who underwent 16 weeks of treatment with lebrikizumab, 68% achieved a 75% reduction in the Eczema Area and Severity Index (EASI-75), interim results from a novel phase 3b trial showed.

Lebrikizumab, a novel monoclonal antibody being developed by Eli Lilly and Co, binds with high affinity to interleukin (IL)–13, thereby blocking the downstream effects of IL-13 with high potency, one of the study investigators, Jill S. Waibel, MD, a dermatologist in Miami, said at the annual meeting of the American Academy of Dermatology. Though the efficacy and safety of lebrikizumab to treat moderate to severe AD have been established in phase 3 studies, including subset analyses by race and ethnicity, “there is a paucity of data to guide the treatment of moderate-to-severe AD in populations traditionally under-represented in clinical trials, including patients with skin of color,” she said.

During a late-breaking abstract session, Dr. Waibel presented interim 16-week results from ADmirable, a phase 3b, open-label, 24-week study, was the first study to evaluate the safety and efficacy of lebrikizumab in adult and adolescents with skin of color and moderate to severe AD. At baseline and at 2 weeks, patients received a 500-mg loading dose of lebrikizumab. Through week 16, they received a 250-mg dose every 2 weeks. The study’s primary endpoint was the proportion of patients who achieved a 75% reduction in EASI-75 at week 16. “If they achieved the primary endpoint at week 16, they went to a 250-mg dose every 4 weeks,” Dr. Waibel said. “If they did not achieve that [primary endpoint] they stayed on the 250-mg dose every 2 weeks.”

The analysis included 50 patients with skin types IV, V, and VI who self-reported their race as Black or African American, American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander. They had chronic AD for at least 1 year, moderate to severe disease at baseline, a history of an inadequate response to topical medications, and were naive to biologics indicated for the treatment of AD.

Week 16 outcomes of interest were the EASI, the Investigator’s Global Assessment (IGA) of 0 or 1, the Pruritus Numerical Rating Scale (NRS), and PDCA-Derm, a scale developed by Eli Lilly and Co that was used to compare postinflammatory lesions to unaffected adjacent normal skin. All data for statistical analyses were summarized as observed.

At baseline, the mean age of the 50 patients was 42 years, 46% were women, their mean body mass index was 30.2, and the mean age at AD onset was 23 years. Most study participants (80%) were Black or African American, 14% were Asian, and 6% were American Indian or Alaska Native; 78% were not Hispanic or Latino and 22% were Hispanic or Latino. The mean EASI score was 28.1, the mean body surface area affected was 41.7%, and the mean Pruritus NRS score was 7.2 out of 11. According to the PDCA-Derm scale, 18% of patients had hypopigmented lesions, and 54% had hyperpigmented lesions.

After 16 weeks of treatment, 68% of patients achieved an EASI-75 response, whereas 46% achieved an EASI-90 response, Dr. Waibel reported at the meeting. In addition, 39% of patients achieved an IGA score of 0 or 1, 56% achieved a ≥ 4-point improvement on the Pruritus NRS, and 66% achieved a ≥ 3-point improvement on the Pruritus NRS. The PDCA-Derm score identified improvement in postinflammatory hyperpigmented lesions in 12 of 21 patients and improvement to normal skin tone in six of 21 patients.

“I have a large population [with skin of color in my practice],” Dr. Waibel said. “I usually tell my [patients with postinflammatory hyperpigmentation] that it takes 6 months to see improvement. In this study, we saw patients achieve improvement in skin tone in a 4-month time frame. PIH is sometimes more distressing than a primary condition, whether it’s acne or atopic dermatitis. In this case, it was surprisingly improved with lebrikizumab.”

No new safety signals or serious adverse events were observed. “This is very exciting because it’s the first time there has been a trial focusing on [patients with skin of color] with moderate to severe eczema in skin types IV-VI,” Dr. Waibel said.

In an interview, the study’s lead investigator, Andrew Alexis, MD, MPH, vice chair for diversity and inclusion in the department of dermatology and professor of clinical dermatology at Weill Cornell Medicine, New York City, said that the interim results from this study “ add valuable, clinically relevant data on the treatment of moderate to severe AD in patient populations with skin of color.”

“An interesting finding,” he continued, “was that improvement in postinflammatory hyperpigmented lesions was seen in 12 of 21 patients and improvement to normal skin tone was observed in six of 21 patients at week 16. This is particularly relevant to patients with skin of color who frequently suffer from pigmentary changes in association with their AD.”

Lebrikizumab was approved in November 2023 in Europe for the treatment of moderate to severe AD in people aged 12 years or older and is currently under review by the Food and Drug Administration for treatment of AD. 

Both Dr. Waibel and Dr. Alexis disclosed numerous conflicts of interest from various pharmaceutical companies, including serving as a consultant and/or advisor to Eli Lilly and Co.
 

A version of this article appeared on Medscape.com.
 

SAN DIEGO — Among patients with skin of color and moderate to severe atopic dermatitis (AD) who underwent 16 weeks of treatment with lebrikizumab, 68% achieved a 75% reduction in the Eczema Area and Severity Index (EASI-75), interim results from a novel phase 3b trial showed.

Lebrikizumab, a novel monoclonal antibody being developed by Eli Lilly and Co, binds with high affinity to interleukin (IL)–13, thereby blocking the downstream effects of IL-13 with high potency, one of the study investigators, Jill S. Waibel, MD, a dermatologist in Miami, said at the annual meeting of the American Academy of Dermatology. Though the efficacy and safety of lebrikizumab to treat moderate to severe AD have been established in phase 3 studies, including subset analyses by race and ethnicity, “there is a paucity of data to guide the treatment of moderate-to-severe AD in populations traditionally under-represented in clinical trials, including patients with skin of color,” she said.

During a late-breaking abstract session, Dr. Waibel presented interim 16-week results from ADmirable, a phase 3b, open-label, 24-week study, was the first study to evaluate the safety and efficacy of lebrikizumab in adult and adolescents with skin of color and moderate to severe AD. At baseline and at 2 weeks, patients received a 500-mg loading dose of lebrikizumab. Through week 16, they received a 250-mg dose every 2 weeks. The study’s primary endpoint was the proportion of patients who achieved a 75% reduction in EASI-75 at week 16. “If they achieved the primary endpoint at week 16, they went to a 250-mg dose every 4 weeks,” Dr. Waibel said. “If they did not achieve that [primary endpoint] they stayed on the 250-mg dose every 2 weeks.”

The analysis included 50 patients with skin types IV, V, and VI who self-reported their race as Black or African American, American Indian or Alaska Native, Asian, and Native Hawaiian or Other Pacific Islander. They had chronic AD for at least 1 year, moderate to severe disease at baseline, a history of an inadequate response to topical medications, and were naive to biologics indicated for the treatment of AD.

Week 16 outcomes of interest were the EASI, the Investigator’s Global Assessment (IGA) of 0 or 1, the Pruritus Numerical Rating Scale (NRS), and PDCA-Derm, a scale developed by Eli Lilly and Co that was used to compare postinflammatory lesions to unaffected adjacent normal skin. All data for statistical analyses were summarized as observed.

At baseline, the mean age of the 50 patients was 42 years, 46% were women, their mean body mass index was 30.2, and the mean age at AD onset was 23 years. Most study participants (80%) were Black or African American, 14% were Asian, and 6% were American Indian or Alaska Native; 78% were not Hispanic or Latino and 22% were Hispanic or Latino. The mean EASI score was 28.1, the mean body surface area affected was 41.7%, and the mean Pruritus NRS score was 7.2 out of 11. According to the PDCA-Derm scale, 18% of patients had hypopigmented lesions, and 54% had hyperpigmented lesions.

After 16 weeks of treatment, 68% of patients achieved an EASI-75 response, whereas 46% achieved an EASI-90 response, Dr. Waibel reported at the meeting. In addition, 39% of patients achieved an IGA score of 0 or 1, 56% achieved a ≥ 4-point improvement on the Pruritus NRS, and 66% achieved a ≥ 3-point improvement on the Pruritus NRS. The PDCA-Derm score identified improvement in postinflammatory hyperpigmented lesions in 12 of 21 patients and improvement to normal skin tone in six of 21 patients.

“I have a large population [with skin of color in my practice],” Dr. Waibel said. “I usually tell my [patients with postinflammatory hyperpigmentation] that it takes 6 months to see improvement. In this study, we saw patients achieve improvement in skin tone in a 4-month time frame. PIH is sometimes more distressing than a primary condition, whether it’s acne or atopic dermatitis. In this case, it was surprisingly improved with lebrikizumab.”

No new safety signals or serious adverse events were observed. “This is very exciting because it’s the first time there has been a trial focusing on [patients with skin of color] with moderate to severe eczema in skin types IV-VI,” Dr. Waibel said.

In an interview, the study’s lead investigator, Andrew Alexis, MD, MPH, vice chair for diversity and inclusion in the department of dermatology and professor of clinical dermatology at Weill Cornell Medicine, New York City, said that the interim results from this study “ add valuable, clinically relevant data on the treatment of moderate to severe AD in patient populations with skin of color.”

“An interesting finding,” he continued, “was that improvement in postinflammatory hyperpigmented lesions was seen in 12 of 21 patients and improvement to normal skin tone was observed in six of 21 patients at week 16. This is particularly relevant to patients with skin of color who frequently suffer from pigmentary changes in association with their AD.”

Lebrikizumab was approved in November 2023 in Europe for the treatment of moderate to severe AD in people aged 12 years or older and is currently under review by the Food and Drug Administration for treatment of AD. 

Both Dr. Waibel and Dr. Alexis disclosed numerous conflicts of interest from various pharmaceutical companies, including serving as a consultant and/or advisor to Eli Lilly and Co.
 

A version of this article appeared on Medscape.com.
 

SAN DIEGO — Home-based phototherapy is non-inferior to office-based phototherapy for the treatment of plaque and guttate psoriasis across all skin types and was associated with improved Physician’s Global Assessment (PGA) and Dermatology Life Quality Index (DLQI) scores, results from a pragmatic, multicenter study showed.

“In 2024, we have a lot of ways to treat moderate-to-severe psoriasis, and phototherapy remains relevant,” lead investigator Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania in Philadelphia, told attendees of a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. 

Courtesy Dr. Gelfand

“Office phototherapy is 10 to 100 times less expensive than biologics for psoriasis, and in head-to-head trials, it’s about as effective as adalimumab and achieves better patient-reported outcomes. It may have some cardiovascular benefits by lowering IL-6 and improving HDL-P,” he said. “And, compared to secukinumab, it has no risk of infection.”

Although phototherapy is a preferred as a treatment by patients with psoriasis, he continued, inconvenience of traveling to a clinician’s office for the treatment and lack of coverage by health insurance plans remain major barriers to this option. According to Dr. Gelfand, office-based phototherapy is not available in 90% of counties in the United States, “and a lack of US data has resulted in many insurance companies not covering home phototherapy. As a result, many providers are uncertain about prescribing it.”
 

LITE Study Data

In 2019, Dr. Gelfand and colleagues Light Treatment Effectiveness (LITE) study, a patient-centered study that tested the hypothesis that narrowband UVB phototherapy of psoriasis at home is non-inferior to office treatment, based on outcomes that matter to patients, clinicians, and payers. The co-primary outcomes were a PGA score of 0/1 (clear, almost clear) and a DLQI score of 5 or less (small, no effect on health-related quality of life).

Dr. Gelfand and colleagues at 42 sites in the United States enrolled 783 patients aged 12 years and older who had plaque or guttate psoriasis and were candidates for phototherapy at home or in an office setting. New or established patients to the practices were accepted into the trial, while those treated with phototherapy within 14 days before the baseline visit were not. These entry criteria “are highly pragmatic and reflect routine clinical practice,” he said.

The researchers evenly stratified patients by skin types I and II, III and IV, and V and VI. They collected data from medical records or from an app on the patient’s cell phone, which captured the DLQI data. Study participants were randomly assigned 1:1 to office- or home-based phototherapy for 12 weeks at doses recommended in the 2019 AAD-National Psoriasis Foundation guidelines. This was followed by a 12-week observation period, which ended at 24 weeks. 

At baseline, the mean DLQI score of patients was 12.2, the mean PGA score was 3, and their mean body surface area affected was 12.5%. “These patients had pretty severe disease, long-standing disease, and about 12% were on biologics or nonbiologic systemic therapy during the study,” said Dr. Gelfand, also the director of the Psoriasis and Phototherapy Treatment Center at Penn. In addition, he said, “the average round-trip to receive phototherapy in the office was about 60 minutes.”
 

An Improvement in Health Equity

Following treatment at 12 weeks, 25.6% of patients in the office-based phototherapy group achieved a PGA of 0/1, compared with 32.8% of patients in the home-based phototherapy group (P >.0001 for non-inferiority). Similarly, 33.6% of patients in the office-based phototherapy group achieved a score of 5 or less on the DLQI, compared with 52.4% of patients in the home-based phototherapy group (P >.0001 for non-inferiority).

In subgroup analyses, patients with darkly pigmented skin did especially well on home phototherapy relative to office treatment. “This finding is an example of how the LITE study was specifically designed to improve health equity through an intentionally inclusive approach,” Dr. Gelfand said. Perhaps not surprisingly, patients in the home-based phototherapy arm were more adherent to treatment compared with those in the office-based arm (a mean of 26.8 sessions during the study period, compared with a mean of 17.9, respectively; P < .0001). “They also had higher cumulative doses of phototherapy and therefore higher episodes of treatments with erythema,” he noted.

Among patients who reported “itchy, sore, painful, or stinging” skin in the previous week, 63% characterized the degree of discomfort as “not at all or a little,” while 28% said “a lot,” and 9% said “very much.” No patients withdrew or stopped phototherapy during the trial because of treatment-related side effects, “so it’s very well tolerated,” Dr. Gelfand said.

“If a patient never had phototherapy before, they did just as well at home as they did in the office. This suggests that there’s no reason to insist that a patient use office-based phototherapy before using home phototherapy.”

The researchers studied the efficacy of narrow-band UVB in patients who had at least two treatments per week for 12 weeks. In this subgroup of patients, 60% achieved clear or almost clear skin and nearly 50% achieved the equivalent of a Psoriasis Area and Severity Index (PASI) 90 score.

“Home phototherapy is clearly non-inferior to office-based phototherapy across all skin types and both primary outcomes, PGA and DLQI, and both have excellent effectiveness and safety in real-world settings,” Dr. Gelfand concluded. “These data support the use of home phototherapy as a first-line treatment option for psoriasis, including those with no prior phototherapy experience.”

LITE Study Described as “Groundbreaking”

One of the session moderators, dermatologist Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, asked about the impact that lockdowns during the early phase of the COVID-19 pandemic had on the trial. “The study shut down for a couple weeks during the initial lockdown, but we got back up and running pretty quickly,” Dr. Gelfand responded. “We didn’t study that specific period of time, but the study was going on well before COVID and well after COVID restrictions were lifted. We’ll have to analyze that period of time you question but I suspect that it’s not driving the results we see.”

Asked to comment, Henry W. Lim, MD, a dermatologist with Henry Ford Health in Detroit, characterized the findings of the study as “groundbreaking, because it looked at a real-life situation in the use of phototherapy at home vs in the office, showing that the home phototherapy is not inferior to office-based phototherapy.”

A version of this article appeared on Medscape.com.

SAN DIEGO — Home-based phototherapy is non-inferior to office-based phototherapy for the treatment of plaque and guttate psoriasis across all skin types and was associated with improved Physician’s Global Assessment (PGA) and Dermatology Life Quality Index (DLQI) scores, results from a pragmatic, multicenter study showed.

“In 2024, we have a lot of ways to treat moderate-to-severe psoriasis, and phototherapy remains relevant,” lead investigator Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania in Philadelphia, told attendees of a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. 

Courtesy Dr. Gelfand

“Office phototherapy is 10 to 100 times less expensive than biologics for psoriasis, and in head-to-head trials, it’s about as effective as adalimumab and achieves better patient-reported outcomes. It may have some cardiovascular benefits by lowering IL-6 and improving HDL-P,” he said. “And, compared to secukinumab, it has no risk of infection.”

Although phototherapy is a preferred as a treatment by patients with psoriasis, he continued, inconvenience of traveling to a clinician’s office for the treatment and lack of coverage by health insurance plans remain major barriers to this option. According to Dr. Gelfand, office-based phototherapy is not available in 90% of counties in the United States, “and a lack of US data has resulted in many insurance companies not covering home phototherapy. As a result, many providers are uncertain about prescribing it.”
 

LITE Study Data

In 2019, Dr. Gelfand and colleagues Light Treatment Effectiveness (LITE) study, a patient-centered study that tested the hypothesis that narrowband UVB phototherapy of psoriasis at home is non-inferior to office treatment, based on outcomes that matter to patients, clinicians, and payers. The co-primary outcomes were a PGA score of 0/1 (clear, almost clear) and a DLQI score of 5 or less (small, no effect on health-related quality of life).

Dr. Gelfand and colleagues at 42 sites in the United States enrolled 783 patients aged 12 years and older who had plaque or guttate psoriasis and were candidates for phototherapy at home or in an office setting. New or established patients to the practices were accepted into the trial, while those treated with phototherapy within 14 days before the baseline visit were not. These entry criteria “are highly pragmatic and reflect routine clinical practice,” he said.

The researchers evenly stratified patients by skin types I and II, III and IV, and V and VI. They collected data from medical records or from an app on the patient’s cell phone, which captured the DLQI data. Study participants were randomly assigned 1:1 to office- or home-based phototherapy for 12 weeks at doses recommended in the 2019 AAD-National Psoriasis Foundation guidelines. This was followed by a 12-week observation period, which ended at 24 weeks. 

At baseline, the mean DLQI score of patients was 12.2, the mean PGA score was 3, and their mean body surface area affected was 12.5%. “These patients had pretty severe disease, long-standing disease, and about 12% were on biologics or nonbiologic systemic therapy during the study,” said Dr. Gelfand, also the director of the Psoriasis and Phototherapy Treatment Center at Penn. In addition, he said, “the average round-trip to receive phototherapy in the office was about 60 minutes.”
 

An Improvement in Health Equity

Following treatment at 12 weeks, 25.6% of patients in the office-based phototherapy group achieved a PGA of 0/1, compared with 32.8% of patients in the home-based phototherapy group (P >.0001 for non-inferiority). Similarly, 33.6% of patients in the office-based phototherapy group achieved a score of 5 or less on the DLQI, compared with 52.4% of patients in the home-based phototherapy group (P >.0001 for non-inferiority).

In subgroup analyses, patients with darkly pigmented skin did especially well on home phototherapy relative to office treatment. “This finding is an example of how the LITE study was specifically designed to improve health equity through an intentionally inclusive approach,” Dr. Gelfand said. Perhaps not surprisingly, patients in the home-based phototherapy arm were more adherent to treatment compared with those in the office-based arm (a mean of 26.8 sessions during the study period, compared with a mean of 17.9, respectively; P < .0001). “They also had higher cumulative doses of phototherapy and therefore higher episodes of treatments with erythema,” he noted.

Among patients who reported “itchy, sore, painful, or stinging” skin in the previous week, 63% characterized the degree of discomfort as “not at all or a little,” while 28% said “a lot,” and 9% said “very much.” No patients withdrew or stopped phototherapy during the trial because of treatment-related side effects, “so it’s very well tolerated,” Dr. Gelfand said.

“If a patient never had phototherapy before, they did just as well at home as they did in the office. This suggests that there’s no reason to insist that a patient use office-based phototherapy before using home phototherapy.”

The researchers studied the efficacy of narrow-band UVB in patients who had at least two treatments per week for 12 weeks. In this subgroup of patients, 60% achieved clear or almost clear skin and nearly 50% achieved the equivalent of a Psoriasis Area and Severity Index (PASI) 90 score.

“Home phototherapy is clearly non-inferior to office-based phototherapy across all skin types and both primary outcomes, PGA and DLQI, and both have excellent effectiveness and safety in real-world settings,” Dr. Gelfand concluded. “These data support the use of home phototherapy as a first-line treatment option for psoriasis, including those with no prior phototherapy experience.”

LITE Study Described as “Groundbreaking”

One of the session moderators, dermatologist Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, asked about the impact that lockdowns during the early phase of the COVID-19 pandemic had on the trial. “The study shut down for a couple weeks during the initial lockdown, but we got back up and running pretty quickly,” Dr. Gelfand responded. “We didn’t study that specific period of time, but the study was going on well before COVID and well after COVID restrictions were lifted. We’ll have to analyze that period of time you question but I suspect that it’s not driving the results we see.”

Asked to comment, Henry W. Lim, MD, a dermatologist with Henry Ford Health in Detroit, characterized the findings of the study as “groundbreaking, because it looked at a real-life situation in the use of phototherapy at home vs in the office, showing that the home phototherapy is not inferior to office-based phototherapy.”

A version of this article appeared on Medscape.com.

SAN DIEGO — Home-based phototherapy is non-inferior to office-based phototherapy for the treatment of plaque and guttate psoriasis across all skin types and was associated with improved Physician’s Global Assessment (PGA) and Dermatology Life Quality Index (DLQI) scores, results from a pragmatic, multicenter study showed.

“In 2024, we have a lot of ways to treat moderate-to-severe psoriasis, and phototherapy remains relevant,” lead investigator Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania in Philadelphia, told attendees of a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. 

Courtesy Dr. Gelfand

“Office phototherapy is 10 to 100 times less expensive than biologics for psoriasis, and in head-to-head trials, it’s about as effective as adalimumab and achieves better patient-reported outcomes. It may have some cardiovascular benefits by lowering IL-6 and improving HDL-P,” he said. “And, compared to secukinumab, it has no risk of infection.”

Although phototherapy is a preferred as a treatment by patients with psoriasis, he continued, inconvenience of traveling to a clinician’s office for the treatment and lack of coverage by health insurance plans remain major barriers to this option. According to Dr. Gelfand, office-based phototherapy is not available in 90% of counties in the United States, “and a lack of US data has resulted in many insurance companies not covering home phototherapy. As a result, many providers are uncertain about prescribing it.”
 

LITE Study Data

In 2019, Dr. Gelfand and colleagues Light Treatment Effectiveness (LITE) study, a patient-centered study that tested the hypothesis that narrowband UVB phototherapy of psoriasis at home is non-inferior to office treatment, based on outcomes that matter to patients, clinicians, and payers. The co-primary outcomes were a PGA score of 0/1 (clear, almost clear) and a DLQI score of 5 or less (small, no effect on health-related quality of life).

Dr. Gelfand and colleagues at 42 sites in the United States enrolled 783 patients aged 12 years and older who had plaque or guttate psoriasis and were candidates for phototherapy at home or in an office setting. New or established patients to the practices were accepted into the trial, while those treated with phototherapy within 14 days before the baseline visit were not. These entry criteria “are highly pragmatic and reflect routine clinical practice,” he said.

The researchers evenly stratified patients by skin types I and II, III and IV, and V and VI. They collected data from medical records or from an app on the patient’s cell phone, which captured the DLQI data. Study participants were randomly assigned 1:1 to office- or home-based phototherapy for 12 weeks at doses recommended in the 2019 AAD-National Psoriasis Foundation guidelines. This was followed by a 12-week observation period, which ended at 24 weeks. 

At baseline, the mean DLQI score of patients was 12.2, the mean PGA score was 3, and their mean body surface area affected was 12.5%. “These patients had pretty severe disease, long-standing disease, and about 12% were on biologics or nonbiologic systemic therapy during the study,” said Dr. Gelfand, also the director of the Psoriasis and Phototherapy Treatment Center at Penn. In addition, he said, “the average round-trip to receive phototherapy in the office was about 60 minutes.”
 

An Improvement in Health Equity

Following treatment at 12 weeks, 25.6% of patients in the office-based phototherapy group achieved a PGA of 0/1, compared with 32.8% of patients in the home-based phototherapy group (P >.0001 for non-inferiority). Similarly, 33.6% of patients in the office-based phototherapy group achieved a score of 5 or less on the DLQI, compared with 52.4% of patients in the home-based phototherapy group (P >.0001 for non-inferiority).

In subgroup analyses, patients with darkly pigmented skin did especially well on home phototherapy relative to office treatment. “This finding is an example of how the LITE study was specifically designed to improve health equity through an intentionally inclusive approach,” Dr. Gelfand said. Perhaps not surprisingly, patients in the home-based phototherapy arm were more adherent to treatment compared with those in the office-based arm (a mean of 26.8 sessions during the study period, compared with a mean of 17.9, respectively; P < .0001). “They also had higher cumulative doses of phototherapy and therefore higher episodes of treatments with erythema,” he noted.

Among patients who reported “itchy, sore, painful, or stinging” skin in the previous week, 63% characterized the degree of discomfort as “not at all or a little,” while 28% said “a lot,” and 9% said “very much.” No patients withdrew or stopped phototherapy during the trial because of treatment-related side effects, “so it’s very well tolerated,” Dr. Gelfand said.

“If a patient never had phototherapy before, they did just as well at home as they did in the office. This suggests that there’s no reason to insist that a patient use office-based phototherapy before using home phototherapy.”

The researchers studied the efficacy of narrow-band UVB in patients who had at least two treatments per week for 12 weeks. In this subgroup of patients, 60% achieved clear or almost clear skin and nearly 50% achieved the equivalent of a Psoriasis Area and Severity Index (PASI) 90 score.

“Home phototherapy is clearly non-inferior to office-based phototherapy across all skin types and both primary outcomes, PGA and DLQI, and both have excellent effectiveness and safety in real-world settings,” Dr. Gelfand concluded. “These data support the use of home phototherapy as a first-line treatment option for psoriasis, including those with no prior phototherapy experience.”

LITE Study Described as “Groundbreaking”

One of the session moderators, dermatologist Andrew Blauvelt, MD, MBA, of the Oregon Medical Research Center, Portland, asked about the impact that lockdowns during the early phase of the COVID-19 pandemic had on the trial. “The study shut down for a couple weeks during the initial lockdown, but we got back up and running pretty quickly,” Dr. Gelfand responded. “We didn’t study that specific period of time, but the study was going on well before COVID and well after COVID restrictions were lifted. We’ll have to analyze that period of time you question but I suspect that it’s not driving the results we see.”

Asked to comment, Henry W. Lim, MD, a dermatologist with Henry Ford Health in Detroit, characterized the findings of the study as “groundbreaking, because it looked at a real-life situation in the use of phototherapy at home vs in the office, showing that the home phototherapy is not inferior to office-based phototherapy.”

A version of this article appeared on Medscape.com.

Medical schools with diversity, equity, and inclusion (DEI) initiatives could lose federal funding under a new bill proposed this week in the US House of Representatives. 

The Embracing Anti-Discrimination, Unbiased Curricula, and Advancing Truth in Education (EDUCATE) Act was introduced March 19 by North Carolina Rep. Greg Murphy (R-NC3). It aims to ban what the bill describes as “race-based mandates” at medical schools. 

The legislation highlights a larger national backlash, largely led by conservatives, against considering race and ethnicity in higher education after the Supreme Court overturned affirmative action last summer. 

According to the bill’s text, medical schools must not “establish, maintain, or contract with a [DEI] office, or any other functional equivalent.” They must also agree that they will not force students or faculty to acknowledge that “America is an oppressive nation” or that “individuals should be adversely treated on the basis of their sex, race, ethnicity, religion, color, or national origin.” 

If H.R. 7725 passes, noncompliant medical schools would no longer receive federal funding or be eligible to participate in guaranteed student loan programs. 

Advocating for colorblind medical school admissions overlooks the racism that still exists in society, said Vanessa Grubbs, MD, MPH, nephrologist and cofounder of the nonprofit Black Doc Village. She told this news organization that bills like H.R. 7725 distract from the real work of diversifying the physician workforce to achieve equitable care for all. 

“There’s a huge body of literature that shows when there is racial or cultural concordance, people have better satisfaction and health outcomes,” said Dr. Grubbs. “It’s really telling that the first thing the people dreaming up these bills say is that by having a diverse workforce, it automatically means that you have a less qualified workforce or that you’re lowering standards.”

The bill joins dozens of state legislative actions seeking to ban DEI principles in healthcare.

This week, Alabama legislators passed a bill prohibiting public universities from establishing DEI programs or using state money to sponsor events involving “divisive concepts.” If signed by the governor, the bill would go into effect on October 1, 2024, joining states like Tennessee and Utah with similar laws already on the books.

Industry groups are also grappling with anti-DEI sentiment. Earlier this month, the American Academy of Dermatology’s annual meeting took an unexpected turn when a member physician and 92 colleagues petitioned the academy to end its DEI programs, including scholarships and mentoring. A committee hearing the petition declined to send it to the Academy’s board.

Rep. Murphy, a urology surgeon who wrote a related editorial in the Wall Street Journal, argued that DEI ideology violates freedom of speech and allows medical schools to reject candidates for not being progressive enough. In the opinion piece, he and coauthor nephrologist Stanley Goldfarb, MD, referred to DEI efforts as “quackery” and a form of discrimination. 

Dr. Goldfarb is the chairman of Do No Harm, a Virginia-based advocacy group that has pushed to eradicate “identity politics” in medical education and clinical practice. The group was instrumental in suing the Louisiana governor for a law requiring that minority candidates fill some state medical board positions. It also filed a complaint against the Medical Board of California on behalf of two physicians, claiming the state’s mandated implicit bias training for healthcare professionals violates their First Amendment rights.

Following the Supreme Court’s ruling overturning affirmative action, the American Medical Association (AMA) adopted a policy advising medical schools to consider race as a factor in admissions alongside other criteria such as test scores, grades, and interviews. The policy provides a “necessary safeguard” to diversify the physician workforce and advance health equity, the AMA said at the time. 

The Association of American Medical Colleges supports DEI principles in medical education while advocating for race-neutral admissions practices like holistic review. This method considers the whole applicant, including their experiences, attributes, academic achievements, and the value they bring to the learning environment. 

H.R. 7725 has 35 cosponsors, many of whom are physicians. Podiatrist and Ohio Rep. Brad Wenstrup (R) said in a statement that medical education should be “free of discrimination” and that the bill would prevent physicians from “being forced to pledge, affirm, or adopt tenets that have infiltrated higher education.”

A version of this article appeared on Medscape.com .

Medical schools with diversity, equity, and inclusion (DEI) initiatives could lose federal funding under a new bill proposed this week in the US House of Representatives. 

The Embracing Anti-Discrimination, Unbiased Curricula, and Advancing Truth in Education (EDUCATE) Act was introduced March 19 by North Carolina Rep. Greg Murphy (R-NC3). It aims to ban what the bill describes as “race-based mandates” at medical schools. 

The legislation highlights a larger national backlash, largely led by conservatives, against considering race and ethnicity in higher education after the Supreme Court overturned affirmative action last summer. 

According to the bill’s text, medical schools must not “establish, maintain, or contract with a [DEI] office, or any other functional equivalent.” They must also agree that they will not force students or faculty to acknowledge that “America is an oppressive nation” or that “individuals should be adversely treated on the basis of their sex, race, ethnicity, religion, color, or national origin.” 

If H.R. 7725 passes, noncompliant medical schools would no longer receive federal funding or be eligible to participate in guaranteed student loan programs. 

Advocating for colorblind medical school admissions overlooks the racism that still exists in society, said Vanessa Grubbs, MD, MPH, nephrologist and cofounder of the nonprofit Black Doc Village. She told this news organization that bills like H.R. 7725 distract from the real work of diversifying the physician workforce to achieve equitable care for all. 

“There’s a huge body of literature that shows when there is racial or cultural concordance, people have better satisfaction and health outcomes,” said Dr. Grubbs. “It’s really telling that the first thing the people dreaming up these bills say is that by having a diverse workforce, it automatically means that you have a less qualified workforce or that you’re lowering standards.”

The bill joins dozens of state legislative actions seeking to ban DEI principles in healthcare.

This week, Alabama legislators passed a bill prohibiting public universities from establishing DEI programs or using state money to sponsor events involving “divisive concepts.” If signed by the governor, the bill would go into effect on October 1, 2024, joining states like Tennessee and Utah with similar laws already on the books.

Industry groups are also grappling with anti-DEI sentiment. Earlier this month, the American Academy of Dermatology’s annual meeting took an unexpected turn when a member physician and 92 colleagues petitioned the academy to end its DEI programs, including scholarships and mentoring. A committee hearing the petition declined to send it to the Academy’s board.

Rep. Murphy, a urology surgeon who wrote a related editorial in the Wall Street Journal, argued that DEI ideology violates freedom of speech and allows medical schools to reject candidates for not being progressive enough. In the opinion piece, he and coauthor nephrologist Stanley Goldfarb, MD, referred to DEI efforts as “quackery” and a form of discrimination. 

Dr. Goldfarb is the chairman of Do No Harm, a Virginia-based advocacy group that has pushed to eradicate “identity politics” in medical education and clinical practice. The group was instrumental in suing the Louisiana governor for a law requiring that minority candidates fill some state medical board positions. It also filed a complaint against the Medical Board of California on behalf of two physicians, claiming the state’s mandated implicit bias training for healthcare professionals violates their First Amendment rights.

Following the Supreme Court’s ruling overturning affirmative action, the American Medical Association (AMA) adopted a policy advising medical schools to consider race as a factor in admissions alongside other criteria such as test scores, grades, and interviews. The policy provides a “necessary safeguard” to diversify the physician workforce and advance health equity, the AMA said at the time. 

The Association of American Medical Colleges supports DEI principles in medical education while advocating for race-neutral admissions practices like holistic review. This method considers the whole applicant, including their experiences, attributes, academic achievements, and the value they bring to the learning environment. 

H.R. 7725 has 35 cosponsors, many of whom are physicians. Podiatrist and Ohio Rep. Brad Wenstrup (R) said in a statement that medical education should be “free of discrimination” and that the bill would prevent physicians from “being forced to pledge, affirm, or adopt tenets that have infiltrated higher education.”

A version of this article appeared on Medscape.com .

Medical schools with diversity, equity, and inclusion (DEI) initiatives could lose federal funding under a new bill proposed this week in the US House of Representatives. 

The Embracing Anti-Discrimination, Unbiased Curricula, and Advancing Truth in Education (EDUCATE) Act was introduced March 19 by North Carolina Rep. Greg Murphy (R-NC3). It aims to ban what the bill describes as “race-based mandates” at medical schools. 

The legislation highlights a larger national backlash, largely led by conservatives, against considering race and ethnicity in higher education after the Supreme Court overturned affirmative action last summer. 

According to the bill’s text, medical schools must not “establish, maintain, or contract with a [DEI] office, or any other functional equivalent.” They must also agree that they will not force students or faculty to acknowledge that “America is an oppressive nation” or that “individuals should be adversely treated on the basis of their sex, race, ethnicity, religion, color, or national origin.” 

If H.R. 7725 passes, noncompliant medical schools would no longer receive federal funding or be eligible to participate in guaranteed student loan programs. 

Advocating for colorblind medical school admissions overlooks the racism that still exists in society, said Vanessa Grubbs, MD, MPH, nephrologist and cofounder of the nonprofit Black Doc Village. She told this news organization that bills like H.R. 7725 distract from the real work of diversifying the physician workforce to achieve equitable care for all. 

“There’s a huge body of literature that shows when there is racial or cultural concordance, people have better satisfaction and health outcomes,” said Dr. Grubbs. “It’s really telling that the first thing the people dreaming up these bills say is that by having a diverse workforce, it automatically means that you have a less qualified workforce or that you’re lowering standards.”

The bill joins dozens of state legislative actions seeking to ban DEI principles in healthcare.

This week, Alabama legislators passed a bill prohibiting public universities from establishing DEI programs or using state money to sponsor events involving “divisive concepts.” If signed by the governor, the bill would go into effect on October 1, 2024, joining states like Tennessee and Utah with similar laws already on the books.

Industry groups are also grappling with anti-DEI sentiment. Earlier this month, the American Academy of Dermatology’s annual meeting took an unexpected turn when a member physician and 92 colleagues petitioned the academy to end its DEI programs, including scholarships and mentoring. A committee hearing the petition declined to send it to the Academy’s board.

Rep. Murphy, a urology surgeon who wrote a related editorial in the Wall Street Journal, argued that DEI ideology violates freedom of speech and allows medical schools to reject candidates for not being progressive enough. In the opinion piece, he and coauthor nephrologist Stanley Goldfarb, MD, referred to DEI efforts as “quackery” and a form of discrimination. 

Dr. Goldfarb is the chairman of Do No Harm, a Virginia-based advocacy group that has pushed to eradicate “identity politics” in medical education and clinical practice. The group was instrumental in suing the Louisiana governor for a law requiring that minority candidates fill some state medical board positions. It also filed a complaint against the Medical Board of California on behalf of two physicians, claiming the state’s mandated implicit bias training for healthcare professionals violates their First Amendment rights.

Following the Supreme Court’s ruling overturning affirmative action, the American Medical Association (AMA) adopted a policy advising medical schools to consider race as a factor in admissions alongside other criteria such as test scores, grades, and interviews. The policy provides a “necessary safeguard” to diversify the physician workforce and advance health equity, the AMA said at the time. 

The Association of American Medical Colleges supports DEI principles in medical education while advocating for race-neutral admissions practices like holistic review. This method considers the whole applicant, including their experiences, attributes, academic achievements, and the value they bring to the learning environment. 

H.R. 7725 has 35 cosponsors, many of whom are physicians. Podiatrist and Ohio Rep. Brad Wenstrup (R) said in a statement that medical education should be “free of discrimination” and that the bill would prevent physicians from “being forced to pledge, affirm, or adopt tenets that have infiltrated higher education.”

A version of this article appeared on Medscape.com .

SAN DIEGO — The investigative oral Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib shows promise in patients with moderate to severe hidradenitis suppurativa (HS), results from a randomized 16-week phase 2 trial showed.

“Research shows that the TNF-alpha and IL-17 signaling pathways have important roles in HS,” lead investigator Alexa B. Kimball, MD, MPH, from the Clinical Laboratory for Epidemiology and Applied Research in Skin at Beth Israel Deaconess Medical Center, Boston, said at the annual meeting of the American Academy of Dermatology. “However, several additional pathways are thought to contribute to disease pathogenesis.”

“We will see if phase 3 trials with more balanced demographics across remibrutinib and placebo arms will reproduce these outcomes,” she continued, “It is exciting to see this potential new medication for HS under continued investigation, especially in light of the current gap in oral therapeutic options for the HS patient community.” Dr. Hsiao was not involved with the study.

Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies, including the receipt of research grants and consulting fees from Novartis. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article appeared on Medscape.com.

SAN DIEGO — The investigative oral Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib shows promise in patients with moderate to severe hidradenitis suppurativa (HS), results from a randomized 16-week phase 2 trial showed.

“Research shows that the TNF-alpha and IL-17 signaling pathways have important roles in HS,” lead investigator Alexa B. Kimball, MD, MPH, from the Clinical Laboratory for Epidemiology and Applied Research in Skin at Beth Israel Deaconess Medical Center, Boston, said at the annual meeting of the American Academy of Dermatology. “However, several additional pathways are thought to contribute to disease pathogenesis.”

“We will see if phase 3 trials with more balanced demographics across remibrutinib and placebo arms will reproduce these outcomes,” she continued, “It is exciting to see this potential new medication for HS under continued investigation, especially in light of the current gap in oral therapeutic options for the HS patient community.” Dr. Hsiao was not involved with the study.

Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies, including the receipt of research grants and consulting fees from Novartis. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article appeared on Medscape.com.

SAN DIEGO — The investigative oral Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib shows promise in patients with moderate to severe hidradenitis suppurativa (HS), results from a randomized 16-week phase 2 trial showed.

“Research shows that the TNF-alpha and IL-17 signaling pathways have important roles in HS,” lead investigator Alexa B. Kimball, MD, MPH, from the Clinical Laboratory for Epidemiology and Applied Research in Skin at Beth Israel Deaconess Medical Center, Boston, said at the annual meeting of the American Academy of Dermatology. “However, several additional pathways are thought to contribute to disease pathogenesis.”

“We will see if phase 3 trials with more balanced demographics across remibrutinib and placebo arms will reproduce these outcomes,” she continued, “It is exciting to see this potential new medication for HS under continued investigation, especially in light of the current gap in oral therapeutic options for the HS patient community.” Dr. Hsiao was not involved with the study.

Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies, including the receipt of research grants and consulting fees from Novartis. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article appeared on Medscape.com.

TOPLINE: 

The results of a recent study suggest that biologics and small molecule inhibitors (SMIs) do not impair the protective effect of COVID-19 vaccine against hospitalization in patients with psoriasis and hidradenitis suppurativa (HS).

METHODOLOGY:

• It remains unknown whether immunomodulatory therapies impair COVID-19 vaccine efficacy and increase hospitalization rates linked to COVID-19 in patients with inflammatory skin conditions such as psoriasis or HS.
• Researchers conducted a cross-sectional study using data from the Epic Cosmos database from January 2020 to October 2023, identifying 30,845 patients with psoriasis or HS.
• Overall, 22,293 patients with documented completion of their primary COVID-19 vaccine series were included in the analysis.
• Of the vaccinated patients, they compared 7046 patients with psoriasis on SMIs and 2033 with psoriasis or HS on biologics with 13,214 patients who did not receive biologics or SMIs.
• The primary outcome was the COVID-19 hospitalization rate.
• Treatment with biologics did not increase COVID-19-related hospitalization rates in vaccinated patients with psoriasis or HS (hospitalization rate, 6.0% for both those taking and those not taking a biologic; P > .99).
• Similarly, hospitalization rates did not significantly differ between vaccinated patients who received SMIs vs those who did not (7.1% vs 6.0%; P = .0596).

IN PRACTICE:

These findings “encourage dermatologists to continue treating [psoriasis]/HS confidently despite the ongoing COVID-19 pandemic,” the authors concluded.

SOURCE:

The study led by Bella R. Lee from Ohio State University Wexner Medical Center, Columbus, was published online on March 13, 2024, in the Journal of the American Academy of Dermatology. 

LIMITATIONS:

Multivariable adjustments could not be performed in this study due to unavailability of individual-level data, and hospital admissions that occurred outside the Epic system were not captured.

DISCLOSURES:

The study did not receive any funding. All authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

The results of a recent study suggest that biologics and small molecule inhibitors (SMIs) do not impair the protective effect of COVID-19 vaccine against hospitalization in patients with psoriasis and hidradenitis suppurativa (HS).

METHODOLOGY:

• It remains unknown whether immunomodulatory therapies impair COVID-19 vaccine efficacy and increase hospitalization rates linked to COVID-19 in patients with inflammatory skin conditions such as psoriasis or HS.
• Researchers conducted a cross-sectional study using data from the Epic Cosmos database from January 2020 to October 2023, identifying 30,845 patients with psoriasis or HS.
• Overall, 22,293 patients with documented completion of their primary COVID-19 vaccine series were included in the analysis.
• Of the vaccinated patients, they compared 7046 patients with psoriasis on SMIs and 2033 with psoriasis or HS on biologics with 13,214 patients who did not receive biologics or SMIs.
• The primary outcome was the COVID-19 hospitalization rate.
• Treatment with biologics did not increase COVID-19-related hospitalization rates in vaccinated patients with psoriasis or HS (hospitalization rate, 6.0% for both those taking and those not taking a biologic; P > .99).
• Similarly, hospitalization rates did not significantly differ between vaccinated patients who received SMIs vs those who did not (7.1% vs 6.0%; P = .0596).

IN PRACTICE:

These findings “encourage dermatologists to continue treating [psoriasis]/HS confidently despite the ongoing COVID-19 pandemic,” the authors concluded.

SOURCE:

The study led by Bella R. Lee from Ohio State University Wexner Medical Center, Columbus, was published online on March 13, 2024, in the Journal of the American Academy of Dermatology. 

LIMITATIONS:

Multivariable adjustments could not be performed in this study due to unavailability of individual-level data, and hospital admissions that occurred outside the Epic system were not captured.

DISCLOSURES:

The study did not receive any funding. All authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

The results of a recent study suggest that biologics and small molecule inhibitors (SMIs) do not impair the protective effect of COVID-19 vaccine against hospitalization in patients with psoriasis and hidradenitis suppurativa (HS).

METHODOLOGY:

• It remains unknown whether immunomodulatory therapies impair COVID-19 vaccine efficacy and increase hospitalization rates linked to COVID-19 in patients with inflammatory skin conditions such as psoriasis or HS.
• Researchers conducted a cross-sectional study using data from the Epic Cosmos database from January 2020 to October 2023, identifying 30,845 patients with psoriasis or HS.
• Overall, 22,293 patients with documented completion of their primary COVID-19 vaccine series were included in the analysis.
• Of the vaccinated patients, they compared 7046 patients with psoriasis on SMIs and 2033 with psoriasis or HS on biologics with 13,214 patients who did not receive biologics or SMIs.
• The primary outcome was the COVID-19 hospitalization rate.
• Treatment with biologics did not increase COVID-19-related hospitalization rates in vaccinated patients with psoriasis or HS (hospitalization rate, 6.0% for both those taking and those not taking a biologic; P > .99).
• Similarly, hospitalization rates did not significantly differ between vaccinated patients who received SMIs vs those who did not (7.1% vs 6.0%; P = .0596).

IN PRACTICE:

These findings “encourage dermatologists to continue treating [psoriasis]/HS confidently despite the ongoing COVID-19 pandemic,” the authors concluded.

SOURCE:

The study led by Bella R. Lee from Ohio State University Wexner Medical Center, Columbus, was published online on March 13, 2024, in the Journal of the American Academy of Dermatology. 

LIMITATIONS:

Multivariable adjustments could not be performed in this study due to unavailability of individual-level data, and hospital admissions that occurred outside the Epic system were not captured.

DISCLOSURES:

The study did not receive any funding. All authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

SAN DIEGO — Maternal hidradenitis suppurativa (HS) is associated with an increased risk for adverse birth outcomes and childhood morbidities, including respiratory, metabolic, central nervous system, and other conditions.

Those are key findings from a longitudinal cohort study that was presented during a poster session at the annual meeting of the American Academy of Dermatology.

“HS is associated with morbidity in women of reproductive age and adverse pregnancy outcomes, [but] its effect on offspring outcomes remains unclear,” corresponding author Kaiyang Li, a third-year medical student at McGill University, Quebec, Canada, and coauthors wrote in their abstract.

To investigate the association between maternal HS and offspring outcomes at birth and with up to 16 years of follow-up, the researchers drew from a longitudinal cohort of 1,275,593 children born in Quebec between April 1, 2006 and March 31, 2022. They matched children with their mothers and used identification numbers to follow the children to note morbidities that led to hospital admissions before age 16 years. The exposure of interest was HS, and the main outcome measure was childhood hospitalizations for respiratory, cardiovascular, metabolic, and other morbidities prior to age 16 years. 

Next, they estimated hazard ratios (HR) and 95% CIs for the association of maternal HS with childhood morbidity in adjusted Cox proportional hazards regression models. “As prenatal exposure to hyperandrogenism may influence boys and girls differently, we carried out subgroup analyses stratified by child sex,” they wrote. 

The study population included 1283 children whose mothers had HS and 1,274,310 unexposed children. As for infant outcomes, compared with no exposure, maternal HS was associated with an increased risk for preterm birth (relative risk [RR], 1.29; 95% CI, 1,08-1.55), neonatal death (RR, 2.07; 95% CI, 1.03-14.13), birth defects (RR, 1.29; 95% CI, 1.07-1.56), congenital heart defects (RR, 1.57; 95% CI, 1.02-2.44), and orofacial defects (RR 4.29; 95% CI, 1.85-9.97).

As for long-term outcomes in the children, compared with those whose mothers did not have HS, maternal HS was associated with an increased risk for any childhood hospitalization (HR, 1.31; 95% CI, 1.19-1.44), respiratory hospitalization (HR, 1.21; 95% CI, 1.05-1.40), metabolic hospitalization (HR, 2.64; 95% CI, 1.67-4.20), gastrointestinal hospitalization (HR, 1.34; 95% CI, 1.03-1.74), and developmental hospitalization (HR, 1.92; 95% CI, 1.43-2.58).

Commenting on the results after the meeting, Ms. Li said that the findings support the need for timely management of HS in expectant mothers and people planning to conceive, and for “interdisciplinary care and follow up for both the mother and the baby, involving the dermatologist, the obstetrician, and the neonatologist or pediatrician if needed.”

“HS is a multidisciplinary disease, plain and simple,” Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, who was asked to comment on the study, said in an interview. “This study highlights the importance of collaboration between dermatology and obstetrician-gynecologist given the potential negative pregnancy outcomes, but to me raising alarm bells given the known gaps and delays in diagnosis matched to disease onset,” said Dr. Friedman, who was not involved with the study. “We need to do better to ensure the safety of both patient and patient-to-be.”

The researchers reported having no financial disclosures. The abstract was selected as the second-place winner in the AAD’s poster competition. Dr. Friedman has no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Maternal hidradenitis suppurativa (HS) is associated with an increased risk for adverse birth outcomes and childhood morbidities, including respiratory, metabolic, central nervous system, and other conditions.

Those are key findings from a longitudinal cohort study that was presented during a poster session at the annual meeting of the American Academy of Dermatology.

“HS is associated with morbidity in women of reproductive age and adverse pregnancy outcomes, [but] its effect on offspring outcomes remains unclear,” corresponding author Kaiyang Li, a third-year medical student at McGill University, Quebec, Canada, and coauthors wrote in their abstract.

To investigate the association between maternal HS and offspring outcomes at birth and with up to 16 years of follow-up, the researchers drew from a longitudinal cohort of 1,275,593 children born in Quebec between April 1, 2006 and March 31, 2022. They matched children with their mothers and used identification numbers to follow the children to note morbidities that led to hospital admissions before age 16 years. The exposure of interest was HS, and the main outcome measure was childhood hospitalizations for respiratory, cardiovascular, metabolic, and other morbidities prior to age 16 years. 

Next, they estimated hazard ratios (HR) and 95% CIs for the association of maternal HS with childhood morbidity in adjusted Cox proportional hazards regression models. “As prenatal exposure to hyperandrogenism may influence boys and girls differently, we carried out subgroup analyses stratified by child sex,” they wrote. 

The study population included 1283 children whose mothers had HS and 1,274,310 unexposed children. As for infant outcomes, compared with no exposure, maternal HS was associated with an increased risk for preterm birth (relative risk [RR], 1.29; 95% CI, 1,08-1.55), neonatal death (RR, 2.07; 95% CI, 1.03-14.13), birth defects (RR, 1.29; 95% CI, 1.07-1.56), congenital heart defects (RR, 1.57; 95% CI, 1.02-2.44), and orofacial defects (RR 4.29; 95% CI, 1.85-9.97).

As for long-term outcomes in the children, compared with those whose mothers did not have HS, maternal HS was associated with an increased risk for any childhood hospitalization (HR, 1.31; 95% CI, 1.19-1.44), respiratory hospitalization (HR, 1.21; 95% CI, 1.05-1.40), metabolic hospitalization (HR, 2.64; 95% CI, 1.67-4.20), gastrointestinal hospitalization (HR, 1.34; 95% CI, 1.03-1.74), and developmental hospitalization (HR, 1.92; 95% CI, 1.43-2.58).

Commenting on the results after the meeting, Ms. Li said that the findings support the need for timely management of HS in expectant mothers and people planning to conceive, and for “interdisciplinary care and follow up for both the mother and the baby, involving the dermatologist, the obstetrician, and the neonatologist or pediatrician if needed.”

“HS is a multidisciplinary disease, plain and simple,” Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, who was asked to comment on the study, said in an interview. “This study highlights the importance of collaboration between dermatology and obstetrician-gynecologist given the potential negative pregnancy outcomes, but to me raising alarm bells given the known gaps and delays in diagnosis matched to disease onset,” said Dr. Friedman, who was not involved with the study. “We need to do better to ensure the safety of both patient and patient-to-be.”

The researchers reported having no financial disclosures. The abstract was selected as the second-place winner in the AAD’s poster competition. Dr. Friedman has no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Maternal hidradenitis suppurativa (HS) is associated with an increased risk for adverse birth outcomes and childhood morbidities, including respiratory, metabolic, central nervous system, and other conditions.

Those are key findings from a longitudinal cohort study that was presented during a poster session at the annual meeting of the American Academy of Dermatology.

“HS is associated with morbidity in women of reproductive age and adverse pregnancy outcomes, [but] its effect on offspring outcomes remains unclear,” corresponding author Kaiyang Li, a third-year medical student at McGill University, Quebec, Canada, and coauthors wrote in their abstract.

To investigate the association between maternal HS and offspring outcomes at birth and with up to 16 years of follow-up, the researchers drew from a longitudinal cohort of 1,275,593 children born in Quebec between April 1, 2006 and March 31, 2022. They matched children with their mothers and used identification numbers to follow the children to note morbidities that led to hospital admissions before age 16 years. The exposure of interest was HS, and the main outcome measure was childhood hospitalizations for respiratory, cardiovascular, metabolic, and other morbidities prior to age 16 years. 

Next, they estimated hazard ratios (HR) and 95% CIs for the association of maternal HS with childhood morbidity in adjusted Cox proportional hazards regression models. “As prenatal exposure to hyperandrogenism may influence boys and girls differently, we carried out subgroup analyses stratified by child sex,” they wrote. 

The study population included 1283 children whose mothers had HS and 1,274,310 unexposed children. As for infant outcomes, compared with no exposure, maternal HS was associated with an increased risk for preterm birth (relative risk [RR], 1.29; 95% CI, 1,08-1.55), neonatal death (RR, 2.07; 95% CI, 1.03-14.13), birth defects (RR, 1.29; 95% CI, 1.07-1.56), congenital heart defects (RR, 1.57; 95% CI, 1.02-2.44), and orofacial defects (RR 4.29; 95% CI, 1.85-9.97).

As for long-term outcomes in the children, compared with those whose mothers did not have HS, maternal HS was associated with an increased risk for any childhood hospitalization (HR, 1.31; 95% CI, 1.19-1.44), respiratory hospitalization (HR, 1.21; 95% CI, 1.05-1.40), metabolic hospitalization (HR, 2.64; 95% CI, 1.67-4.20), gastrointestinal hospitalization (HR, 1.34; 95% CI, 1.03-1.74), and developmental hospitalization (HR, 1.92; 95% CI, 1.43-2.58).

Commenting on the results after the meeting, Ms. Li said that the findings support the need for timely management of HS in expectant mothers and people planning to conceive, and for “interdisciplinary care and follow up for both the mother and the baby, involving the dermatologist, the obstetrician, and the neonatologist or pediatrician if needed.”

“HS is a multidisciplinary disease, plain and simple,” Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, who was asked to comment on the study, said in an interview. “This study highlights the importance of collaboration between dermatology and obstetrician-gynecologist given the potential negative pregnancy outcomes, but to me raising alarm bells given the known gaps and delays in diagnosis matched to disease onset,” said Dr. Friedman, who was not involved with the study. “We need to do better to ensure the safety of both patient and patient-to-be.”

The researchers reported having no financial disclosures. The abstract was selected as the second-place winner in the AAD’s poster competition. Dr. Friedman has no relevant disclosures.

A version of this article appeared on Medscape.com.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

A recent study linking a niacin derivative to an increased risk for cardiovascular events has raised questions about the safety of this B vitamin, which is added to many food staples in the Western diet and taken in the form of supplements.

The findings, which were published in Nature Medicine, may also help explain why taking niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events in major clinical trials.

But could this essential micronutrient really have an adverse effect on cardiovascular risk, and what are the implications for niacin intake?

Senior author of the new study Stanley Hazen, MD, believes some prudence on excessive niacin intake may be justified.

“I’m not suggesting we should completely avoid niacin — it is an essential nutrient, but our results suggest that too much may be harmful,” Dr. Hazen said.

Niacin supplements are also sold with claims of antiaging effects, arthritis relief, and boosting brain function, although none of these claims have been proven. And the related compound, nicotinamide, is recommended to prevent skin cancer in high-risk patients; however, a recent study questioned that guidance.

“I would say to the general public that avoiding supplements containing niacin or related compounds could be a sensible approach at present, while these findings are investigated further.”

Other experts are unsure if such action is justified on the basis of this single study.
 

Residual Cardiovascular Risk

Dr. Hazen, who is chair of the Department of Cardiovascular & Metabolic Sciences, at the Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, explained to this news organization that they did not set out to study niacin.

“It began as a study to look for novel pathways involved in residual cardiovascular disease risk — the risk for cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

The researchers began looking for compounds in plasma that predicted future adverse cardiovascular events in individuals undergoing elective diagnostic cardiac evaluation. Two of the leading candidates identified were niacin derivatives — 2PY and 4PY — that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts — 2331 US individuals and a European cohort of 832 individuals. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling in cardiovascular risk seen in those with levels in the highest vs the lowest quartile.

To move beyond these observational studies and to explore a potentially causal relationship, Dr. Hazen’s team went on to perform genome-wide association studies and found that genetic variants that tracked with higher levels of 4PY also linked to levels of the inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1).

And in cell culture and animal studies, they found that 4PY was a driver of inflammation, upregulating VCAM-1 and eliciting vascular inflammation responses.

“So, we have shown in several different ways that the niacin derivative, 4PY, is linked to increased cardiovascular risk,” Dr. Hazen commented.
 

Significant Health Implications?

Dr. Hazen believed these findings could have significant health implications.

He noted that Western populations have been consuming large amounts of niacin ever since World War 2 when we began to fortify many foods with essential vitamins to avoid diseases caused by deficiencies. Niacin was added to foods to prevent pellagra — a disease characterized by inflamed skin, diarrhea, and dementia, that was often fatal.

“While we may have eliminated pellagra, have we, as a consequence, increased the prevalence of cardiovascular disease many years later?” Dr. Hazen asked.

This may be a clue to why niacin does not lower cardiovascular risk as much as would be expected from the degree of cholesterol lowering it brings about. “This is the niacin paradox and has led to the thought that there could be some kind of adverse effect that niacin is promoting. I think we may have found something that contributes to the niacin paradox,” he said.

However, the niacin pathway is complicated. Niacin is the major source of nicotinamide adenine dinucleotide (NAD), an integral molecule that allows cells to create energy. “Because it is so important, our bodies are designed to salvage and retain NADs, but once storage capacity is exceeded, then these 4PY and 2PY derivatives are generated,” Dr. Hazen explained. “But you have to really eat a lot of niacin-rich foods for this to happen.”

He is not claiming that niacin causes cardiovascular disease. “It is 4PY that appears to be the driver of vascular inflammation. And 4PY is a breakdown product of niacin. But there is more than one pathway that could lead to 4PY generation. There is a whole interconnecting network of compounds that interchange with each other — known as the niacin pool — any one or more of these compounds can be ingested and raise pool levels and ultimately 4PY levels. However, by far and away, niacin is one of the major sources,” Dr. Hazen commented.
 

Are High-Protein Diets Also Implicated?

Other sources of NADs include tryptophan, present in protein. And one of the genetic variants linked to changes in 4PY levels is connected to how dietary protein is directed into the niacin pool, raising the possibility that a high-protein diet may also raise cardiovascular risk in some people, Dr. Hazen noted.

Dr. Hazen estimated that about 3% of the niacin pool in a normal diet comes from protein intake, but that the percentage could increase substantially in very high–protein diets.

“Our data support the concept that if we lower our 4PY level long-term, then that would result in a reduction in cardiovascular disease. But this is still just a hypothesis. If we lower niacin intake, we will lower 4PY,” Dr. Hazen stated.

He said that this research is at too early a stage to give firm recommendations in what this means for the consumer.

“Based on these findings, I would advise people to avoid taking niacin or nicotinic acid or nicotinamide supplements and to eat a sensible balanced diet — maybe not to overdo the high protein–type diets. That’s all we can really say at the moment.”

Noting that niacin can also be one of the major components in energy drinks, he suggested it may be prudent to limit consumption of these products.
 

What Is the Optimum Niacin Intake?

Dr. Hazen noted that the recommended dietary allowance (RDA) for niacin is well known — between 14 and 18 mg, but he said the average American ingests four times that amount, and some people have substantially higher intakes — up to 50 times the RDA if taking supplements.

While food fortification with niacin may have been useful in the past, Dr. Hazen questioned whether it should still be mandated.

“In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin has led to an increase in cardiovascular disease?”

He does not propose stopping all niacin fortification, “but maybe, we could have the choice of selecting an unfortified option,” he said.
 

Causal Link Not Proven

Commenting for this news organization, John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed “interesting and important results,” but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.

“These findings need to be investigated further, and more studies are certainly justified, but I don’t think that this study alone makes an adequate case for restricting niacin intake, or thinking about stopping niacin fortification of foodstuffs,” Dr. Guyton said.

Noting that niacin is present in large quantities in many fast foods, he suggested the researchers may have just picked up the consequences of eating an unhealthy diet.

“If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet,” he commented.

Dr. Guyton also pointed out that major clinical trials with niacin have shown mixed results, and its effect on cardiovascular risk is still not completely understood. While the HPS2-THRIVE and AIM-HIGH trials did not show benefits in reducing cardiovascular events, an earlier study, the Coronary Drug Project in which the agent was given with food, did show some positive effects with substantial reductions in myocardial infarction and stroke, and there was the suggestion of a reduction in long-term mortality in the niacin group several years after the trial had ended.
 

Nicotinamide in Skin Cancer Prevention

What about the use of nicotinamide in skin cancer prevention?

Addressing this question, Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, pointed out that nicotinamide, although closely related to niacin, may have different effects. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, professor of dermatology at the University of Sydney, Camperdown, Australia, told this news organization that it was hard to extrapolate these findings on basal levels of niacin in a cardiac cohort to the administration of supra-physiological doses of nicotinamide for skin cancer prevention.

There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin, Dr. Damian said, adding that it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.

She pointed out that high vs low levels of nicotinamide supplementation can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. At high doses, nicotinamide is anti-inflammatory in skin.

Dr. Damian noted that two phase 3 studies (ONTRAC and ONTRANS) of nicotinamide 500 mg twice daily for skin cancer prevention did not find a significant increase in cardiovascular events compared to placebo over 12 months.

“Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,” she commented.

“For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,” she added.

Meanwhile, Dr. Hazen said the most exciting part of this new research is the discovery of a new pathway that contributes to cardiovascular disease and potentially a new target to treat residual cardiovascular risk.

“I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk.”

The next step will be to confirm these results in other populations and then to develop a diagnostic test to identify people with a high 4PY level, he said.

A version of this article appeared on Medscape.com.

A recent study linking a niacin derivative to an increased risk for cardiovascular events has raised questions about the safety of this B vitamin, which is added to many food staples in the Western diet and taken in the form of supplements.

The findings, which were published in Nature Medicine, may also help explain why taking niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events in major clinical trials.

But could this essential micronutrient really have an adverse effect on cardiovascular risk, and what are the implications for niacin intake?

Senior author of the new study Stanley Hazen, MD, believes some prudence on excessive niacin intake may be justified.

“I’m not suggesting we should completely avoid niacin — it is an essential nutrient, but our results suggest that too much may be harmful,” Dr. Hazen said.

Niacin supplements are also sold with claims of antiaging effects, arthritis relief, and boosting brain function, although none of these claims have been proven. And the related compound, nicotinamide, is recommended to prevent skin cancer in high-risk patients; however, a recent study questioned that guidance.

“I would say to the general public that avoiding supplements containing niacin or related compounds could be a sensible approach at present, while these findings are investigated further.”

Other experts are unsure if such action is justified on the basis of this single study.
 

Residual Cardiovascular Risk

Dr. Hazen, who is chair of the Department of Cardiovascular & Metabolic Sciences, at the Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, explained to this news organization that they did not set out to study niacin.

“It began as a study to look for novel pathways involved in residual cardiovascular disease risk — the risk for cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

The researchers began looking for compounds in plasma that predicted future adverse cardiovascular events in individuals undergoing elective diagnostic cardiac evaluation. Two of the leading candidates identified were niacin derivatives — 2PY and 4PY — that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts — 2331 US individuals and a European cohort of 832 individuals. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling in cardiovascular risk seen in those with levels in the highest vs the lowest quartile.

To move beyond these observational studies and to explore a potentially causal relationship, Dr. Hazen’s team went on to perform genome-wide association studies and found that genetic variants that tracked with higher levels of 4PY also linked to levels of the inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1).

And in cell culture and animal studies, they found that 4PY was a driver of inflammation, upregulating VCAM-1 and eliciting vascular inflammation responses.

“So, we have shown in several different ways that the niacin derivative, 4PY, is linked to increased cardiovascular risk,” Dr. Hazen commented.
 

Significant Health Implications?

Dr. Hazen believed these findings could have significant health implications.

He noted that Western populations have been consuming large amounts of niacin ever since World War 2 when we began to fortify many foods with essential vitamins to avoid diseases caused by deficiencies. Niacin was added to foods to prevent pellagra — a disease characterized by inflamed skin, diarrhea, and dementia, that was often fatal.

“While we may have eliminated pellagra, have we, as a consequence, increased the prevalence of cardiovascular disease many years later?” Dr. Hazen asked.

This may be a clue to why niacin does not lower cardiovascular risk as much as would be expected from the degree of cholesterol lowering it brings about. “This is the niacin paradox and has led to the thought that there could be some kind of adverse effect that niacin is promoting. I think we may have found something that contributes to the niacin paradox,” he said.

However, the niacin pathway is complicated. Niacin is the major source of nicotinamide adenine dinucleotide (NAD), an integral molecule that allows cells to create energy. “Because it is so important, our bodies are designed to salvage and retain NADs, but once storage capacity is exceeded, then these 4PY and 2PY derivatives are generated,” Dr. Hazen explained. “But you have to really eat a lot of niacin-rich foods for this to happen.”

He is not claiming that niacin causes cardiovascular disease. “It is 4PY that appears to be the driver of vascular inflammation. And 4PY is a breakdown product of niacin. But there is more than one pathway that could lead to 4PY generation. There is a whole interconnecting network of compounds that interchange with each other — known as the niacin pool — any one or more of these compounds can be ingested and raise pool levels and ultimately 4PY levels. However, by far and away, niacin is one of the major sources,” Dr. Hazen commented.
 

Are High-Protein Diets Also Implicated?

Other sources of NADs include tryptophan, present in protein. And one of the genetic variants linked to changes in 4PY levels is connected to how dietary protein is directed into the niacin pool, raising the possibility that a high-protein diet may also raise cardiovascular risk in some people, Dr. Hazen noted.

Dr. Hazen estimated that about 3% of the niacin pool in a normal diet comes from protein intake, but that the percentage could increase substantially in very high–protein diets.

“Our data support the concept that if we lower our 4PY level long-term, then that would result in a reduction in cardiovascular disease. But this is still just a hypothesis. If we lower niacin intake, we will lower 4PY,” Dr. Hazen stated.

He said that this research is at too early a stage to give firm recommendations in what this means for the consumer.

“Based on these findings, I would advise people to avoid taking niacin or nicotinic acid or nicotinamide supplements and to eat a sensible balanced diet — maybe not to overdo the high protein–type diets. That’s all we can really say at the moment.”

Noting that niacin can also be one of the major components in energy drinks, he suggested it may be prudent to limit consumption of these products.
 

What Is the Optimum Niacin Intake?

Dr. Hazen noted that the recommended dietary allowance (RDA) for niacin is well known — between 14 and 18 mg, but he said the average American ingests four times that amount, and some people have substantially higher intakes — up to 50 times the RDA if taking supplements.

While food fortification with niacin may have been useful in the past, Dr. Hazen questioned whether it should still be mandated.

“In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin has led to an increase in cardiovascular disease?”

He does not propose stopping all niacin fortification, “but maybe, we could have the choice of selecting an unfortified option,” he said.
 

Causal Link Not Proven

Commenting for this news organization, John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed “interesting and important results,” but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.

“These findings need to be investigated further, and more studies are certainly justified, but I don’t think that this study alone makes an adequate case for restricting niacin intake, or thinking about stopping niacin fortification of foodstuffs,” Dr. Guyton said.

Noting that niacin is present in large quantities in many fast foods, he suggested the researchers may have just picked up the consequences of eating an unhealthy diet.

“If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet,” he commented.

Dr. Guyton also pointed out that major clinical trials with niacin have shown mixed results, and its effect on cardiovascular risk is still not completely understood. While the HPS2-THRIVE and AIM-HIGH trials did not show benefits in reducing cardiovascular events, an earlier study, the Coronary Drug Project in which the agent was given with food, did show some positive effects with substantial reductions in myocardial infarction and stroke, and there was the suggestion of a reduction in long-term mortality in the niacin group several years after the trial had ended.
 

Nicotinamide in Skin Cancer Prevention

What about the use of nicotinamide in skin cancer prevention?

Addressing this question, Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, pointed out that nicotinamide, although closely related to niacin, may have different effects. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, professor of dermatology at the University of Sydney, Camperdown, Australia, told this news organization that it was hard to extrapolate these findings on basal levels of niacin in a cardiac cohort to the administration of supra-physiological doses of nicotinamide for skin cancer prevention.

There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin, Dr. Damian said, adding that it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.

She pointed out that high vs low levels of nicotinamide supplementation can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. At high doses, nicotinamide is anti-inflammatory in skin.

Dr. Damian noted that two phase 3 studies (ONTRAC and ONTRANS) of nicotinamide 500 mg twice daily for skin cancer prevention did not find a significant increase in cardiovascular events compared to placebo over 12 months.

“Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,” she commented.

“For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,” she added.

Meanwhile, Dr. Hazen said the most exciting part of this new research is the discovery of a new pathway that contributes to cardiovascular disease and potentially a new target to treat residual cardiovascular risk.

“I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk.”

The next step will be to confirm these results in other populations and then to develop a diagnostic test to identify people with a high 4PY level, he said.

A version of this article appeared on Medscape.com.

A recent study linking a niacin derivative to an increased risk for cardiovascular events has raised questions about the safety of this B vitamin, which is added to many food staples in the Western diet and taken in the form of supplements.

The findings, which were published in Nature Medicine, may also help explain why taking niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events in major clinical trials.

But could this essential micronutrient really have an adverse effect on cardiovascular risk, and what are the implications for niacin intake?

Senior author of the new study Stanley Hazen, MD, believes some prudence on excessive niacin intake may be justified.

“I’m not suggesting we should completely avoid niacin — it is an essential nutrient, but our results suggest that too much may be harmful,” Dr. Hazen said.

Niacin supplements are also sold with claims of antiaging effects, arthritis relief, and boosting brain function, although none of these claims have been proven. And the related compound, nicotinamide, is recommended to prevent skin cancer in high-risk patients; however, a recent study questioned that guidance.

“I would say to the general public that avoiding supplements containing niacin or related compounds could be a sensible approach at present, while these findings are investigated further.”

Other experts are unsure if such action is justified on the basis of this single study.
 

Residual Cardiovascular Risk

Dr. Hazen, who is chair of the Department of Cardiovascular & Metabolic Sciences, at the Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, explained to this news organization that they did not set out to study niacin.

“It began as a study to look for novel pathways involved in residual cardiovascular disease risk — the risk for cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

The researchers began looking for compounds in plasma that predicted future adverse cardiovascular events in individuals undergoing elective diagnostic cardiac evaluation. Two of the leading candidates identified were niacin derivatives — 2PY and 4PY — that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts — 2331 US individuals and a European cohort of 832 individuals. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling in cardiovascular risk seen in those with levels in the highest vs the lowest quartile.

To move beyond these observational studies and to explore a potentially causal relationship, Dr. Hazen’s team went on to perform genome-wide association studies and found that genetic variants that tracked with higher levels of 4PY also linked to levels of the inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1).

And in cell culture and animal studies, they found that 4PY was a driver of inflammation, upregulating VCAM-1 and eliciting vascular inflammation responses.

“So, we have shown in several different ways that the niacin derivative, 4PY, is linked to increased cardiovascular risk,” Dr. Hazen commented.
 

Significant Health Implications?

Dr. Hazen believed these findings could have significant health implications.

He noted that Western populations have been consuming large amounts of niacin ever since World War 2 when we began to fortify many foods with essential vitamins to avoid diseases caused by deficiencies. Niacin was added to foods to prevent pellagra — a disease characterized by inflamed skin, diarrhea, and dementia, that was often fatal.

“While we may have eliminated pellagra, have we, as a consequence, increased the prevalence of cardiovascular disease many years later?” Dr. Hazen asked.

This may be a clue to why niacin does not lower cardiovascular risk as much as would be expected from the degree of cholesterol lowering it brings about. “This is the niacin paradox and has led to the thought that there could be some kind of adverse effect that niacin is promoting. I think we may have found something that contributes to the niacin paradox,” he said.

However, the niacin pathway is complicated. Niacin is the major source of nicotinamide adenine dinucleotide (NAD), an integral molecule that allows cells to create energy. “Because it is so important, our bodies are designed to salvage and retain NADs, but once storage capacity is exceeded, then these 4PY and 2PY derivatives are generated,” Dr. Hazen explained. “But you have to really eat a lot of niacin-rich foods for this to happen.”

He is not claiming that niacin causes cardiovascular disease. “It is 4PY that appears to be the driver of vascular inflammation. And 4PY is a breakdown product of niacin. But there is more than one pathway that could lead to 4PY generation. There is a whole interconnecting network of compounds that interchange with each other — known as the niacin pool — any one or more of these compounds can be ingested and raise pool levels and ultimately 4PY levels. However, by far and away, niacin is one of the major sources,” Dr. Hazen commented.
 

Are High-Protein Diets Also Implicated?

Other sources of NADs include tryptophan, present in protein. And one of the genetic variants linked to changes in 4PY levels is connected to how dietary protein is directed into the niacin pool, raising the possibility that a high-protein diet may also raise cardiovascular risk in some people, Dr. Hazen noted.

Dr. Hazen estimated that about 3% of the niacin pool in a normal diet comes from protein intake, but that the percentage could increase substantially in very high–protein diets.

“Our data support the concept that if we lower our 4PY level long-term, then that would result in a reduction in cardiovascular disease. But this is still just a hypothesis. If we lower niacin intake, we will lower 4PY,” Dr. Hazen stated.

He said that this research is at too early a stage to give firm recommendations in what this means for the consumer.

“Based on these findings, I would advise people to avoid taking niacin or nicotinic acid or nicotinamide supplements and to eat a sensible balanced diet — maybe not to overdo the high protein–type diets. That’s all we can really say at the moment.”

Noting that niacin can also be one of the major components in energy drinks, he suggested it may be prudent to limit consumption of these products.
 

What Is the Optimum Niacin Intake?

Dr. Hazen noted that the recommended dietary allowance (RDA) for niacin is well known — between 14 and 18 mg, but he said the average American ingests four times that amount, and some people have substantially higher intakes — up to 50 times the RDA if taking supplements.

While food fortification with niacin may have been useful in the past, Dr. Hazen questioned whether it should still be mandated.

“In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin has led to an increase in cardiovascular disease?”

He does not propose stopping all niacin fortification, “but maybe, we could have the choice of selecting an unfortified option,” he said.
 

Causal Link Not Proven

Commenting for this news organization, John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed “interesting and important results,” but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.

“These findings need to be investigated further, and more studies are certainly justified, but I don’t think that this study alone makes an adequate case for restricting niacin intake, or thinking about stopping niacin fortification of foodstuffs,” Dr. Guyton said.

Noting that niacin is present in large quantities in many fast foods, he suggested the researchers may have just picked up the consequences of eating an unhealthy diet.

“If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet,” he commented.

Dr. Guyton also pointed out that major clinical trials with niacin have shown mixed results, and its effect on cardiovascular risk is still not completely understood. While the HPS2-THRIVE and AIM-HIGH trials did not show benefits in reducing cardiovascular events, an earlier study, the Coronary Drug Project in which the agent was given with food, did show some positive effects with substantial reductions in myocardial infarction and stroke, and there was the suggestion of a reduction in long-term mortality in the niacin group several years after the trial had ended.
 

Nicotinamide in Skin Cancer Prevention

What about the use of nicotinamide in skin cancer prevention?

Addressing this question, Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, pointed out that nicotinamide, although closely related to niacin, may have different effects. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, professor of dermatology at the University of Sydney, Camperdown, Australia, told this news organization that it was hard to extrapolate these findings on basal levels of niacin in a cardiac cohort to the administration of supra-physiological doses of nicotinamide for skin cancer prevention.

There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin, Dr. Damian said, adding that it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.

She pointed out that high vs low levels of nicotinamide supplementation can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. At high doses, nicotinamide is anti-inflammatory in skin.

Dr. Damian noted that two phase 3 studies (ONTRAC and ONTRANS) of nicotinamide 500 mg twice daily for skin cancer prevention did not find a significant increase in cardiovascular events compared to placebo over 12 months.

“Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,” she commented.

“For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,” she added.

Meanwhile, Dr. Hazen said the most exciting part of this new research is the discovery of a new pathway that contributes to cardiovascular disease and potentially a new target to treat residual cardiovascular risk.

“I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk.”

The next step will be to confirm these results in other populations and then to develop a diagnostic test to identify people with a high 4PY level, he said.

A version of this article appeared on Medscape.com.