Dermatology News

The recent approval of the first oral fecal-derived microbiota therapy to prevent the recurrence of Clostridioides difficile (C. diff) infection in patients was welcome news for physicians who’ve struggled under the weight of having too few treatment options for the prevention of C. diff recurrence.

The product, developed by Massachusetts-based Seres Therepeutics and marketed as Vowst, was approved by the U.S. Food and Drug Administration on April 26. It is approved for use in adults who have already been treated with antibiotics for a recurrent infection with C. diff bacteria.

This is the first oral treatment for the prevention of C. diff recurrence and is designed to be delivered in four capsules taken daily for 3 days.

Gastroenterologist Phillip I. Tarr, MD, division chief of gastroenterology at Washington University, St. Louis, and chair of the American Gastroenterological Association Center for Gut Microbiome Research and Education, said that prevention of recurrent C. diff infection “remains challenging,” and that Vowst “provides the first FDA-approved, orally administered microbiome therapeutic with which to achieve this goal. This advance also makes us optimistic we might soon be able to prevent other disorders by managing gut microbial communities.”

Vowst is the second therapy derived from human stool to be approved for the indication in less than 6 months. In December, the FDA approved Rebyota (Ferring), a rectally delivered treatment that also uses microbes from donor feces. Both products were given priority review, orphan drug, and breakthrough therapy designations by the agency.

C. diff infection can be aggravated by an alteration of normal gut flora associated with antibiotics treatment, leading to cycles of repeated infections. Infection can produce diarrhea, abdominal pain, fever, and severe morbidity. In the United States, an estimated 15,000 to 30,000 deaths per year are linked to C. diff. Risk factors for recurrent infection include being 65 or older, hospitalization, being in a nursing home, a weakened immune system, and previous infection with C. diff.

Therapies transplanting fecal microbiota from donors have been used since the 1950s as treatments for recurrent C. diff infection, and in the past decade, as stool banks recruiting screened donors have made fecal microbiota transplants, or FMT, standard of care. However, only in recent years have fecal-derived therapies become subject to standardized safety and efficacy testing.

Both the current FDA-approved products, Rebyota and Vowst, were shown in randomized controlled trials to reduce recurrence of C. diff infection, compared with placebo. In a phase 3 clinical trial of Rebyota (n = 262) in antibiotic-treated patients, one rectally administered dose reduced recurrence of C. diff infection by 70.6% at 8 weeks, compared with 57.5% for placebo. A phase 3 study of Vowst (n = 281) showed recurrence in treated subjects to be 12.4% at 8 weeks, compared with nearly 40% of those receiving placebo (relative risk, 0.32; 95% confidence interval, 0.18-0.58; P less than .001).

Despite screening protocols that have become increasingly homogenized and rigorous, FMT is associated with the risk of introducing pathogens. Vowst is manufactured with purified bacterial spores derived from donor feces, not whole stool. Nonetheless, FDA noted in its statement that Vowst could still potentially introduce infectious agents or allergens.
 

Antibiotics are still first-line treatment

In an interview, Jessica Allegretti, MD, MPH, AGAF, medical director of the Crohn’s and Colitis Center at Brigham & Women’s Hospital, Boston, said that having two FDA-approved therapies with different means of administration “is great for the field and great for patients. These are both meant to be used after a course of antibiotics, so antibiotics are still the mainstay of treatment for C. diff and recurrent C. diff, but we now have more options to prevent recurrence.”

The convenience of an oral therapy that can be taken at home is “very attractive,” Dr. Allegretti added, noting that there will also be patients “who either don’t want to or can’t take capsules, for whom a rectal administration [in a health care setting] may be preferred.”

Dr. Allegretti, who has used FMT to treat recurrent C. difficile for more than a decade, said that she expected traditional FMT using screened donor stool to remain available even as the new products are adopted by clinicians. FMT centers like OpenBiome “will continue to provide access for patients who either don’t have the ability to get the FDA-approved products because of insurance coverage, or for financial reasons, or maybe neither of the new products is appropriate for them,” she said. “I do think there will always be a need for the traditional option. The more options that we have available the better.”

TD Cowen analyst Joseph Thome told Reuters that the drug could be priced close to $20,000 per course, expecting peak sales of $750 million in the U.S. in 2033.

Dr. Allegretti disclosed consulting work for Seres Therapeutics, Ferring, and other manufacturers. She is a member of OpenBiome’s clinical advisory board.

The recent approval of the first oral fecal-derived microbiota therapy to prevent the recurrence of Clostridioides difficile (C. diff) infection in patients was welcome news for physicians who’ve struggled under the weight of having too few treatment options for the prevention of C. diff recurrence.

The product, developed by Massachusetts-based Seres Therepeutics and marketed as Vowst, was approved by the U.S. Food and Drug Administration on April 26. It is approved for use in adults who have already been treated with antibiotics for a recurrent infection with C. diff bacteria.

This is the first oral treatment for the prevention of C. diff recurrence and is designed to be delivered in four capsules taken daily for 3 days.

Gastroenterologist Phillip I. Tarr, MD, division chief of gastroenterology at Washington University, St. Louis, and chair of the American Gastroenterological Association Center for Gut Microbiome Research and Education, said that prevention of recurrent C. diff infection “remains challenging,” and that Vowst “provides the first FDA-approved, orally administered microbiome therapeutic with which to achieve this goal. This advance also makes us optimistic we might soon be able to prevent other disorders by managing gut microbial communities.”

Vowst is the second therapy derived from human stool to be approved for the indication in less than 6 months. In December, the FDA approved Rebyota (Ferring), a rectally delivered treatment that also uses microbes from donor feces. Both products were given priority review, orphan drug, and breakthrough therapy designations by the agency.

C. diff infection can be aggravated by an alteration of normal gut flora associated with antibiotics treatment, leading to cycles of repeated infections. Infection can produce diarrhea, abdominal pain, fever, and severe morbidity. In the United States, an estimated 15,000 to 30,000 deaths per year are linked to C. diff. Risk factors for recurrent infection include being 65 or older, hospitalization, being in a nursing home, a weakened immune system, and previous infection with C. diff.

Therapies transplanting fecal microbiota from donors have been used since the 1950s as treatments for recurrent C. diff infection, and in the past decade, as stool banks recruiting screened donors have made fecal microbiota transplants, or FMT, standard of care. However, only in recent years have fecal-derived therapies become subject to standardized safety and efficacy testing.

Both the current FDA-approved products, Rebyota and Vowst, were shown in randomized controlled trials to reduce recurrence of C. diff infection, compared with placebo. In a phase 3 clinical trial of Rebyota (n = 262) in antibiotic-treated patients, one rectally administered dose reduced recurrence of C. diff infection by 70.6% at 8 weeks, compared with 57.5% for placebo. A phase 3 study of Vowst (n = 281) showed recurrence in treated subjects to be 12.4% at 8 weeks, compared with nearly 40% of those receiving placebo (relative risk, 0.32; 95% confidence interval, 0.18-0.58; P less than .001).

Despite screening protocols that have become increasingly homogenized and rigorous, FMT is associated with the risk of introducing pathogens. Vowst is manufactured with purified bacterial spores derived from donor feces, not whole stool. Nonetheless, FDA noted in its statement that Vowst could still potentially introduce infectious agents or allergens.
 

Antibiotics are still first-line treatment

In an interview, Jessica Allegretti, MD, MPH, AGAF, medical director of the Crohn’s and Colitis Center at Brigham & Women’s Hospital, Boston, said that having two FDA-approved therapies with different means of administration “is great for the field and great for patients. These are both meant to be used after a course of antibiotics, so antibiotics are still the mainstay of treatment for C. diff and recurrent C. diff, but we now have more options to prevent recurrence.”

The convenience of an oral therapy that can be taken at home is “very attractive,” Dr. Allegretti added, noting that there will also be patients “who either don’t want to or can’t take capsules, for whom a rectal administration [in a health care setting] may be preferred.”

Dr. Allegretti, who has used FMT to treat recurrent C. difficile for more than a decade, said that she expected traditional FMT using screened donor stool to remain available even as the new products are adopted by clinicians. FMT centers like OpenBiome “will continue to provide access for patients who either don’t have the ability to get the FDA-approved products because of insurance coverage, or for financial reasons, or maybe neither of the new products is appropriate for them,” she said. “I do think there will always be a need for the traditional option. The more options that we have available the better.”

TD Cowen analyst Joseph Thome told Reuters that the drug could be priced close to $20,000 per course, expecting peak sales of $750 million in the U.S. in 2033.

Dr. Allegretti disclosed consulting work for Seres Therapeutics, Ferring, and other manufacturers. She is a member of OpenBiome’s clinical advisory board.

The recent approval of the first oral fecal-derived microbiota therapy to prevent the recurrence of Clostridioides difficile (C. diff) infection in patients was welcome news for physicians who’ve struggled under the weight of having too few treatment options for the prevention of C. diff recurrence.

The product, developed by Massachusetts-based Seres Therepeutics and marketed as Vowst, was approved by the U.S. Food and Drug Administration on April 26. It is approved for use in adults who have already been treated with antibiotics for a recurrent infection with C. diff bacteria.

This is the first oral treatment for the prevention of C. diff recurrence and is designed to be delivered in four capsules taken daily for 3 days.

Gastroenterologist Phillip I. Tarr, MD, division chief of gastroenterology at Washington University, St. Louis, and chair of the American Gastroenterological Association Center for Gut Microbiome Research and Education, said that prevention of recurrent C. diff infection “remains challenging,” and that Vowst “provides the first FDA-approved, orally administered microbiome therapeutic with which to achieve this goal. This advance also makes us optimistic we might soon be able to prevent other disorders by managing gut microbial communities.”

Vowst is the second therapy derived from human stool to be approved for the indication in less than 6 months. In December, the FDA approved Rebyota (Ferring), a rectally delivered treatment that also uses microbes from donor feces. Both products were given priority review, orphan drug, and breakthrough therapy designations by the agency.

C. diff infection can be aggravated by an alteration of normal gut flora associated with antibiotics treatment, leading to cycles of repeated infections. Infection can produce diarrhea, abdominal pain, fever, and severe morbidity. In the United States, an estimated 15,000 to 30,000 deaths per year are linked to C. diff. Risk factors for recurrent infection include being 65 or older, hospitalization, being in a nursing home, a weakened immune system, and previous infection with C. diff.

Therapies transplanting fecal microbiota from donors have been used since the 1950s as treatments for recurrent C. diff infection, and in the past decade, as stool banks recruiting screened donors have made fecal microbiota transplants, or FMT, standard of care. However, only in recent years have fecal-derived therapies become subject to standardized safety and efficacy testing.

Both the current FDA-approved products, Rebyota and Vowst, were shown in randomized controlled trials to reduce recurrence of C. diff infection, compared with placebo. In a phase 3 clinical trial of Rebyota (n = 262) in antibiotic-treated patients, one rectally administered dose reduced recurrence of C. diff infection by 70.6% at 8 weeks, compared with 57.5% for placebo. A phase 3 study of Vowst (n = 281) showed recurrence in treated subjects to be 12.4% at 8 weeks, compared with nearly 40% of those receiving placebo (relative risk, 0.32; 95% confidence interval, 0.18-0.58; P less than .001).

Despite screening protocols that have become increasingly homogenized and rigorous, FMT is associated with the risk of introducing pathogens. Vowst is manufactured with purified bacterial spores derived from donor feces, not whole stool. Nonetheless, FDA noted in its statement that Vowst could still potentially introduce infectious agents or allergens.
 

Antibiotics are still first-line treatment

In an interview, Jessica Allegretti, MD, MPH, AGAF, medical director of the Crohn’s and Colitis Center at Brigham & Women’s Hospital, Boston, said that having two FDA-approved therapies with different means of administration “is great for the field and great for patients. These are both meant to be used after a course of antibiotics, so antibiotics are still the mainstay of treatment for C. diff and recurrent C. diff, but we now have more options to prevent recurrence.”

The convenience of an oral therapy that can be taken at home is “very attractive,” Dr. Allegretti added, noting that there will also be patients “who either don’t want to or can’t take capsules, for whom a rectal administration [in a health care setting] may be preferred.”

Dr. Allegretti, who has used FMT to treat recurrent C. difficile for more than a decade, said that she expected traditional FMT using screened donor stool to remain available even as the new products are adopted by clinicians. FMT centers like OpenBiome “will continue to provide access for patients who either don’t have the ability to get the FDA-approved products because of insurance coverage, or for financial reasons, or maybe neither of the new products is appropriate for them,” she said. “I do think there will always be a need for the traditional option. The more options that we have available the better.”

TD Cowen analyst Joseph Thome told Reuters that the drug could be priced close to $20,000 per course, expecting peak sales of $750 million in the U.S. in 2033.

Dr. Allegretti disclosed consulting work for Seres Therapeutics, Ferring, and other manufacturers. She is a member of OpenBiome’s clinical advisory board.

The Food and Drug Administration has approved injectable poly-L-lactic acid (PLLA-SCA) for the correction of fine lines and wrinkles in the cheek, the manufacturer announced on April 26.

The treatment, marketed as Sculptra, is the first FDA-approved PLLA collagen stimulator that, “when injected into the cheek area, helps stimulate natural collagen production to smooth wrinkles and improve skin quality such as firmness and glow,” according to a press release from the manufacturer, Galderma. Sculptra was first approved for aesthetic use in 2009 in the United States and is now available in more than 40 countries.

Olivier Le Moal/Getty Images

With this expanded approval, PLLA-SCA is now indicated for use in people with healthy immune systems for correcting shallow to deep nasolabial fold contour deficiencies, fine lines, and wrinkles in the cheeks and other facial areas.
 

94% have enduring improvement at 2 years

In a clinical trial, PLLA-SCA achieved the primary efficacy endpoint of at least a 1-grade improvement in wrinkles on both cheeks concurrently at rest and its secondary endpoint of improving cheek wrinkles when smiling for up to 2 years, the company states.

According to Galderma, patients showed aesthetic improvement in cheek wrinkles throughout the study; 96% showed improvement at 3 months, 94% showed improvement at 1 year, and 94% showed improvement at 2 years.

The most common side effects after initial treatment are injection site swelling, tenderness, redness, pain, bruising, bleeding, itching, and lumps, according to the company. Other side effects may include small lumps under the skin that are sometimes noticeable when pressing on the treated area. 

PLLA-SCA is available only through a licensed practitioner and should not be used by people allergic to any ingredient of the product or who have a history of keloid formation or hypertrophic scarring. The company notes that safety has not been established in patients who are pregnant, lactating, breastfeeding, or younger than 18.

In its instruction to clinicians, the company warns the treatment should not be injected into the blood vessels “as it may cause vascular occlusion, infarction, or embolic phenomena.”

Skin sores, cysts, pimples, rashes, hives, or infection should be healed completely before injecting the treatment, the company cautions. PLLA-SCA should not be injected into the red area of the lip or in the periorbital area.

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

The Food and Drug Administration has approved injectable poly-L-lactic acid (PLLA-SCA) for the correction of fine lines and wrinkles in the cheek, the manufacturer announced on April 26.

The treatment, marketed as Sculptra, is the first FDA-approved PLLA collagen stimulator that, “when injected into the cheek area, helps stimulate natural collagen production to smooth wrinkles and improve skin quality such as firmness and glow,” according to a press release from the manufacturer, Galderma. Sculptra was first approved for aesthetic use in 2009 in the United States and is now available in more than 40 countries.

Olivier Le Moal/Getty Images

With this expanded approval, PLLA-SCA is now indicated for use in people with healthy immune systems for correcting shallow to deep nasolabial fold contour deficiencies, fine lines, and wrinkles in the cheeks and other facial areas.
 

94% have enduring improvement at 2 years

In a clinical trial, PLLA-SCA achieved the primary efficacy endpoint of at least a 1-grade improvement in wrinkles on both cheeks concurrently at rest and its secondary endpoint of improving cheek wrinkles when smiling for up to 2 years, the company states.

According to Galderma, patients showed aesthetic improvement in cheek wrinkles throughout the study; 96% showed improvement at 3 months, 94% showed improvement at 1 year, and 94% showed improvement at 2 years.

The most common side effects after initial treatment are injection site swelling, tenderness, redness, pain, bruising, bleeding, itching, and lumps, according to the company. Other side effects may include small lumps under the skin that are sometimes noticeable when pressing on the treated area. 

PLLA-SCA is available only through a licensed practitioner and should not be used by people allergic to any ingredient of the product or who have a history of keloid formation or hypertrophic scarring. The company notes that safety has not been established in patients who are pregnant, lactating, breastfeeding, or younger than 18.

In its instruction to clinicians, the company warns the treatment should not be injected into the blood vessels “as it may cause vascular occlusion, infarction, or embolic phenomena.”

Skin sores, cysts, pimples, rashes, hives, or infection should be healed completely before injecting the treatment, the company cautions. PLLA-SCA should not be injected into the red area of the lip or in the periorbital area.

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

The Food and Drug Administration has approved injectable poly-L-lactic acid (PLLA-SCA) for the correction of fine lines and wrinkles in the cheek, the manufacturer announced on April 26.

The treatment, marketed as Sculptra, is the first FDA-approved PLLA collagen stimulator that, “when injected into the cheek area, helps stimulate natural collagen production to smooth wrinkles and improve skin quality such as firmness and glow,” according to a press release from the manufacturer, Galderma. Sculptra was first approved for aesthetic use in 2009 in the United States and is now available in more than 40 countries.

Olivier Le Moal/Getty Images

With this expanded approval, PLLA-SCA is now indicated for use in people with healthy immune systems for correcting shallow to deep nasolabial fold contour deficiencies, fine lines, and wrinkles in the cheeks and other facial areas.
 

94% have enduring improvement at 2 years

In a clinical trial, PLLA-SCA achieved the primary efficacy endpoint of at least a 1-grade improvement in wrinkles on both cheeks concurrently at rest and its secondary endpoint of improving cheek wrinkles when smiling for up to 2 years, the company states.

According to Galderma, patients showed aesthetic improvement in cheek wrinkles throughout the study; 96% showed improvement at 3 months, 94% showed improvement at 1 year, and 94% showed improvement at 2 years.

The most common side effects after initial treatment are injection site swelling, tenderness, redness, pain, bruising, bleeding, itching, and lumps, according to the company. Other side effects may include small lumps under the skin that are sometimes noticeable when pressing on the treated area. 

PLLA-SCA is available only through a licensed practitioner and should not be used by people allergic to any ingredient of the product or who have a history of keloid formation or hypertrophic scarring. The company notes that safety has not been established in patients who are pregnant, lactating, breastfeeding, or younger than 18.

In its instruction to clinicians, the company warns the treatment should not be injected into the blood vessels “as it may cause vascular occlusion, infarction, or embolic phenomena.”

Skin sores, cysts, pimples, rashes, hives, or infection should be healed completely before injecting the treatment, the company cautions. PLLA-SCA should not be injected into the red area of the lip or in the periorbital area.

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

PHOENIX – Combining a serum containing silymarin with nonablative laser therapy could serve as a promising solution for decreasing inflammation, postinflammatory erythema (PIE), and postinflammatory hyperpigmentation (PIH) associated with acne lesions, results from a prospective, single-center study showed.

“Acne vulgaris is the most common inflammatory dermatosis worldwide, often resulting in sequelae such as scarring, PIE, and PIH,” presenting author Jamie Hu, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study results were presented during an abstract session. “This dyschromia can cause greater psychological distress than the original acne lesions, and disproportionately affects skin of color patients.”

Blemish-prone skin is known to have higher levels of sebum and lower levels of antioxidants, leading to lipid peroxidation and oxidative stress, resulting in proliferation of Cutibacterium acnes and an inflammatory cascade that has recently been implicated in postinflammatory dyschromia and the development of PIE and PIH, noted Dr. Hu, a dermatology resident at the University of Miami. “Therefore, the use of antioxidants presents an opportunity to disrupt blemish and dyschromia,” she said.

One such antioxidant is silymarin, which is derived from the milk thistle plant. Recent studies have demonstrated that silymarin reduces proinflammatory mediators, prevents lipid peroxidation, and presents a new way to target the treatment of both acne and postinflammatory dyschromia.

Dr. Hu’s mentor, Jill S. Waibel, MD, owner and medical director of the Miami Dermatology and Laser Institute, hypothesized that nonablative laser therapy followed by topical application of silymarin would improve acne-associated postinflammatory dyschromia. To test her hunch, she conducted a 12-week, prospective trial in which 24 patients with PIE and/or PIH were randomized to one of two treatment arms: laser treatment with topical antioxidants or laser treatment with vehicle control. Patients received three laser treatments, each 1 month apart. The topical antioxidant used was Silymarin CF, a serum that contains 0.5% silymarin, 0.5% salicylic acid, 15% L-ascorbic acid, and 0.5% ferulic acid. (The study was sponsored by SkinCeuticals, the manufacturer of the serum.)

Laser selection was made primarily on the type of dyschromia, with PIE patients receiving treatment with the pulsed dye laser and PIH patients receiving treatment with the 1,927-nm thulium laser. Patients were treated on days 0, 28, and 56 of the 12-week study, followed by immediate application of topical antioxidants or vehicle control. They were also instructed to apply the assigned topical twice daily for the duration of the study. Patients ranged in age from 21 to 61 years, and 20 had skin types III-IV.

To evaluate efficacy, the researchers conducted blinded clinical assessments with the postacne hyperpigmentation index (PAHPI) and the Global Aesthetic Improvement Scale (GAIS), instrumentation with the Mexameter, a device that captures erythema and melanin index values, and visual diagnostics with optical coherence tomography (OCT).

Dr. Hu reported that at week 12, the PAHPI in the silymarin-plus-laser treatment group fell from an average of 3.18 to 1.74 (a decrease of 1.44), which suggested an improvement trend, compared with the laser treatment–only group, whose PAHPI fell from an average of 3.25 to 1.97 (a decrease of 1.28).

As for the GAIS, a one-time score assessed at the end of the trial, the average score for all patients was 3.24, which translated to “much improved/very much improved.” Patients in the silymarin-plus-laser treatment group had higher average scores compared with patients in the laser treatment–only group (3.35 vs. 3.10, respectively), but the differences did not reach statistical significance.

According to results of the Mexameter assessment, paired t-tests showed that the levels of intralesional melanin decreased significantly for patients in the silymarin-plus-laser treatment group, compared with the laser treatment–only group (P < .05). OCT assessments demonstrated an increase in dermal brightness in both groups, corresponding to an increase in dermal collagen, as well as an increase in blood vessel density.

In an interview at the meeting, Dr. Waibel, subsection chief of dermatology at Baptist Hospital of Miami, said that future studies will focus on long-term follow-up to determine if acne scars can be prevented by combining silymarin with lasers to prevent PIH and PIE. “That would be priceless,” she said. “I believe that the PIH is what causes damage to the collagen, and that damage to the collagen is what causes the scarring. So, if we can prevent or treat PIH, we may be able to prevent scarring.”

This approach, she added, “would decrease the pharmaceutical cost because I think there are many dermatologists who are treating PEI and PIH as active acne. You really have to have a keen eye for understanding the differences and you really have to be looking, because PIE and PIH are flat, whereas active acne consists of either comedones or nodules.”

She noted that in skin of color patients, she has seen PIH persist for 9 or 10 months after treatment with isotretinoin. “It’s not the isotretinoin causing the scars, or even the acne, it’s the prolonged inflammation,” she said.

Catherine M. DiGiorgio, MD, a Boston-based laser and cosmetic dermatologist who was asked to comment on the study, said that patients and dermatologists frequently seek alternatives to hydroquinone for unwanted hyperpigmentation.

Dr. DiGiorgio

Dr. Jalian

“While the study failed to show statistically significant improvement in postinflammatory erythema with concomitant laser and topical therapy versus laser alone, the promising data supporting concurrent use of topicals and fractional lasers for treatment of PIH, particularly in dark skin phototypes, is a clinically impactful contribution to our daily practice,” he said.

Dr. Waibel disclosed that she has conducted clinical trials for many device and pharmaceutical companies including SkinCeuticals. Dr. Hu, Dr. DiGiorgio, and Dr. Jalian were not involved with the study and reported having no relevant disclosures.

PHOENIX – Combining a serum containing silymarin with nonablative laser therapy could serve as a promising solution for decreasing inflammation, postinflammatory erythema (PIE), and postinflammatory hyperpigmentation (PIH) associated with acne lesions, results from a prospective, single-center study showed.

“Acne vulgaris is the most common inflammatory dermatosis worldwide, often resulting in sequelae such as scarring, PIE, and PIH,” presenting author Jamie Hu, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study results were presented during an abstract session. “This dyschromia can cause greater psychological distress than the original acne lesions, and disproportionately affects skin of color patients.”

Blemish-prone skin is known to have higher levels of sebum and lower levels of antioxidants, leading to lipid peroxidation and oxidative stress, resulting in proliferation of Cutibacterium acnes and an inflammatory cascade that has recently been implicated in postinflammatory dyschromia and the development of PIE and PIH, noted Dr. Hu, a dermatology resident at the University of Miami. “Therefore, the use of antioxidants presents an opportunity to disrupt blemish and dyschromia,” she said.

One such antioxidant is silymarin, which is derived from the milk thistle plant. Recent studies have demonstrated that silymarin reduces proinflammatory mediators, prevents lipid peroxidation, and presents a new way to target the treatment of both acne and postinflammatory dyschromia.

Dr. Hu’s mentor, Jill S. Waibel, MD, owner and medical director of the Miami Dermatology and Laser Institute, hypothesized that nonablative laser therapy followed by topical application of silymarin would improve acne-associated postinflammatory dyschromia. To test her hunch, she conducted a 12-week, prospective trial in which 24 patients with PIE and/or PIH were randomized to one of two treatment arms: laser treatment with topical antioxidants or laser treatment with vehicle control. Patients received three laser treatments, each 1 month apart. The topical antioxidant used was Silymarin CF, a serum that contains 0.5% silymarin, 0.5% salicylic acid, 15% L-ascorbic acid, and 0.5% ferulic acid. (The study was sponsored by SkinCeuticals, the manufacturer of the serum.)

Laser selection was made primarily on the type of dyschromia, with PIE patients receiving treatment with the pulsed dye laser and PIH patients receiving treatment with the 1,927-nm thulium laser. Patients were treated on days 0, 28, and 56 of the 12-week study, followed by immediate application of topical antioxidants or vehicle control. They were also instructed to apply the assigned topical twice daily for the duration of the study. Patients ranged in age from 21 to 61 years, and 20 had skin types III-IV.

To evaluate efficacy, the researchers conducted blinded clinical assessments with the postacne hyperpigmentation index (PAHPI) and the Global Aesthetic Improvement Scale (GAIS), instrumentation with the Mexameter, a device that captures erythema and melanin index values, and visual diagnostics with optical coherence tomography (OCT).

Dr. Hu reported that at week 12, the PAHPI in the silymarin-plus-laser treatment group fell from an average of 3.18 to 1.74 (a decrease of 1.44), which suggested an improvement trend, compared with the laser treatment–only group, whose PAHPI fell from an average of 3.25 to 1.97 (a decrease of 1.28).

As for the GAIS, a one-time score assessed at the end of the trial, the average score for all patients was 3.24, which translated to “much improved/very much improved.” Patients in the silymarin-plus-laser treatment group had higher average scores compared with patients in the laser treatment–only group (3.35 vs. 3.10, respectively), but the differences did not reach statistical significance.

According to results of the Mexameter assessment, paired t-tests showed that the levels of intralesional melanin decreased significantly for patients in the silymarin-plus-laser treatment group, compared with the laser treatment–only group (P < .05). OCT assessments demonstrated an increase in dermal brightness in both groups, corresponding to an increase in dermal collagen, as well as an increase in blood vessel density.

In an interview at the meeting, Dr. Waibel, subsection chief of dermatology at Baptist Hospital of Miami, said that future studies will focus on long-term follow-up to determine if acne scars can be prevented by combining silymarin with lasers to prevent PIH and PIE. “That would be priceless,” she said. “I believe that the PIH is what causes damage to the collagen, and that damage to the collagen is what causes the scarring. So, if we can prevent or treat PIH, we may be able to prevent scarring.”

This approach, she added, “would decrease the pharmaceutical cost because I think there are many dermatologists who are treating PEI and PIH as active acne. You really have to have a keen eye for understanding the differences and you really have to be looking, because PIE and PIH are flat, whereas active acne consists of either comedones or nodules.”

She noted that in skin of color patients, she has seen PIH persist for 9 or 10 months after treatment with isotretinoin. “It’s not the isotretinoin causing the scars, or even the acne, it’s the prolonged inflammation,” she said.

Catherine M. DiGiorgio, MD, a Boston-based laser and cosmetic dermatologist who was asked to comment on the study, said that patients and dermatologists frequently seek alternatives to hydroquinone for unwanted hyperpigmentation.

Dr. DiGiorgio

Dr. Jalian

“While the study failed to show statistically significant improvement in postinflammatory erythema with concomitant laser and topical therapy versus laser alone, the promising data supporting concurrent use of topicals and fractional lasers for treatment of PIH, particularly in dark skin phototypes, is a clinically impactful contribution to our daily practice,” he said.

Dr. Waibel disclosed that she has conducted clinical trials for many device and pharmaceutical companies including SkinCeuticals. Dr. Hu, Dr. DiGiorgio, and Dr. Jalian were not involved with the study and reported having no relevant disclosures.

PHOENIX – Combining a serum containing silymarin with nonablative laser therapy could serve as a promising solution for decreasing inflammation, postinflammatory erythema (PIE), and postinflammatory hyperpigmentation (PIH) associated with acne lesions, results from a prospective, single-center study showed.

“Acne vulgaris is the most common inflammatory dermatosis worldwide, often resulting in sequelae such as scarring, PIE, and PIH,” presenting author Jamie Hu, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study results were presented during an abstract session. “This dyschromia can cause greater psychological distress than the original acne lesions, and disproportionately affects skin of color patients.”

Blemish-prone skin is known to have higher levels of sebum and lower levels of antioxidants, leading to lipid peroxidation and oxidative stress, resulting in proliferation of Cutibacterium acnes and an inflammatory cascade that has recently been implicated in postinflammatory dyschromia and the development of PIE and PIH, noted Dr. Hu, a dermatology resident at the University of Miami. “Therefore, the use of antioxidants presents an opportunity to disrupt blemish and dyschromia,” she said.

One such antioxidant is silymarin, which is derived from the milk thistle plant. Recent studies have demonstrated that silymarin reduces proinflammatory mediators, prevents lipid peroxidation, and presents a new way to target the treatment of both acne and postinflammatory dyschromia.

Dr. Hu’s mentor, Jill S. Waibel, MD, owner and medical director of the Miami Dermatology and Laser Institute, hypothesized that nonablative laser therapy followed by topical application of silymarin would improve acne-associated postinflammatory dyschromia. To test her hunch, she conducted a 12-week, prospective trial in which 24 patients with PIE and/or PIH were randomized to one of two treatment arms: laser treatment with topical antioxidants or laser treatment with vehicle control. Patients received three laser treatments, each 1 month apart. The topical antioxidant used was Silymarin CF, a serum that contains 0.5% silymarin, 0.5% salicylic acid, 15% L-ascorbic acid, and 0.5% ferulic acid. (The study was sponsored by SkinCeuticals, the manufacturer of the serum.)

Laser selection was made primarily on the type of dyschromia, with PIE patients receiving treatment with the pulsed dye laser and PIH patients receiving treatment with the 1,927-nm thulium laser. Patients were treated on days 0, 28, and 56 of the 12-week study, followed by immediate application of topical antioxidants or vehicle control. They were also instructed to apply the assigned topical twice daily for the duration of the study. Patients ranged in age from 21 to 61 years, and 20 had skin types III-IV.

To evaluate efficacy, the researchers conducted blinded clinical assessments with the postacne hyperpigmentation index (PAHPI) and the Global Aesthetic Improvement Scale (GAIS), instrumentation with the Mexameter, a device that captures erythema and melanin index values, and visual diagnostics with optical coherence tomography (OCT).

Dr. Hu reported that at week 12, the PAHPI in the silymarin-plus-laser treatment group fell from an average of 3.18 to 1.74 (a decrease of 1.44), which suggested an improvement trend, compared with the laser treatment–only group, whose PAHPI fell from an average of 3.25 to 1.97 (a decrease of 1.28).

As for the GAIS, a one-time score assessed at the end of the trial, the average score for all patients was 3.24, which translated to “much improved/very much improved.” Patients in the silymarin-plus-laser treatment group had higher average scores compared with patients in the laser treatment–only group (3.35 vs. 3.10, respectively), but the differences did not reach statistical significance.

According to results of the Mexameter assessment, paired t-tests showed that the levels of intralesional melanin decreased significantly for patients in the silymarin-plus-laser treatment group, compared with the laser treatment–only group (P < .05). OCT assessments demonstrated an increase in dermal brightness in both groups, corresponding to an increase in dermal collagen, as well as an increase in blood vessel density.

In an interview at the meeting, Dr. Waibel, subsection chief of dermatology at Baptist Hospital of Miami, said that future studies will focus on long-term follow-up to determine if acne scars can be prevented by combining silymarin with lasers to prevent PIH and PIE. “That would be priceless,” she said. “I believe that the PIH is what causes damage to the collagen, and that damage to the collagen is what causes the scarring. So, if we can prevent or treat PIH, we may be able to prevent scarring.”

This approach, she added, “would decrease the pharmaceutical cost because I think there are many dermatologists who are treating PEI and PIH as active acne. You really have to have a keen eye for understanding the differences and you really have to be looking, because PIE and PIH are flat, whereas active acne consists of either comedones or nodules.”

She noted that in skin of color patients, she has seen PIH persist for 9 or 10 months after treatment with isotretinoin. “It’s not the isotretinoin causing the scars, or even the acne, it’s the prolonged inflammation,” she said.

Catherine M. DiGiorgio, MD, a Boston-based laser and cosmetic dermatologist who was asked to comment on the study, said that patients and dermatologists frequently seek alternatives to hydroquinone for unwanted hyperpigmentation.

Dr. DiGiorgio

Dr. Jalian

“While the study failed to show statistically significant improvement in postinflammatory erythema with concomitant laser and topical therapy versus laser alone, the promising data supporting concurrent use of topicals and fractional lasers for treatment of PIH, particularly in dark skin phototypes, is a clinically impactful contribution to our daily practice,” he said.

Dr. Waibel disclosed that she has conducted clinical trials for many device and pharmaceutical companies including SkinCeuticals. Dr. Hu, Dr. DiGiorgio, and Dr. Jalian were not involved with the study and reported having no relevant disclosures.

Taking a swing against arthritis

Osteoarthritis is a tough disease to manage. Exercise helps ease the stiffness and pain of the joints, but at the same time, the disease makes it difficult to do that beneficial exercise. Even a relatively simple activity like jogging can hurt more than it helps. If only there were a low-impact exercise that was incredibly popular among the generally older population who are likely to have arthritis.

We love a good golf study here at LOTME, and a group of Australian and U.K. researchers have provided. Osteoarthritis affects 2 million people in the land down under, making it the most common source of disability there. In that population, only 64% reported their physical health to be good, very good, or excellent. Among the 459 golfers with OA that the study authors surveyed, however, the percentage reporting good health rose to more than 90%.

jacoblund/Getty Images

A similar story emerged when they looked at mental health. Nearly a quarter of nongolfers with OA reported high or very high levels of psychological distress, compared with just 8% of golfers. This pattern of improved physical and mental health remained when the researchers looked at the general, non-OA population.

This isn’t the first time golf’s been connected with improved health, and previous studies have shown golf to reduce the risks of cardiovascular disease, diabetes, and obesity, among other things. Just walking one 18-hole round significantly exceeds the CDC’s recommended 150 minutes of physical activity per week. Go out multiple times a week – leaving the cart and beer at home, American golfers – and you’ll be fit for a lifetime.

The golfers on our staff, however, are still waiting for those mental health benefits to kick in. Because when we’re adding up our scorecard after that string of four double bogeys to end the round, we’re most definitely thinking: “Yes, this sport is reducing my psychological distress. I am having fun right now.”
 

Battle of the sexes’ intestines

There are, we’re sure you’ve noticed, some differences between males and females. Females, for one thing, have longer small intestines than males. Everybody knows that, right? You didn’t know? Really? … Really?

Afif Ramdhasuma/Unsplash

Well, then, we’re guessing you haven’t read “Hidden diversity: Comparative functional morphology of humans and other species” by Erin A. McKenney, PhD, of North Carolina State University, Raleigh, and associates, which just appeared in PeerJ. We couldn’t put it down, even in the shower – a real page-turner/scroller. (It’s a great way to clean a phone, for those who also like to scroll, text, or talk on the toilet.)

The researchers got out their rulers, calipers, and string and took many measurements of the digestive systems of 45 human cadavers (21 female and 24 male), which were compared with data from 10 rats, 10 pigs, and 10 bullfrogs, which had been collected (the measurements, not the animals) by undergraduate students enrolled in a comparative anatomy laboratory course at the university.

There was little intestinal-length variation among the four-legged subjects, but when it comes to humans, females have “consistently and significantly longer small intestines than males,” the investigators noted.

The women’s small intestines, almost 14 feet long on average, were about a foot longer than the men’s, which suggests that women are better able to extract nutrients from food and “supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” coauthor Amanda Hale said in a written statement from the school. The way to a man’s heart may be through his stomach, but the way to a woman’s heart is through her duodenum, it seems.

Fascinating stuff, to be sure, but the thing that really caught our eye in the PeerJ article was the authors’ suggestion “that organs behave independently of one another, both within and across species.” Organs behaving independently? A somewhat ominous concept, no doubt, but it does explain a lot of the sounds we hear coming from our guts, which can get pretty frightening, especially on chili night.
 

Dog walking is dangerous business

Yes, you did read that right. A lot of strange things can send you to the emergency department. Go ahead and add dog walking onto that list.

Investigators from Johns Hopkins University estimate that over 422,000 adults presented to U.S. emergency departments with leash-dependent dog walking-related injuries between 2001 and 2020.

freestocks/Unsplash

With almost 53% of U.S. households owning at least one dog in 2021-2022 in the wake of the COVID pet boom, this kind of occurrence is becoming more common than you think. The annual number of dog-walking injuries more than quadrupled from 7,300 to 32,000 over the course of the study, and the researchers link that spike to the promotion of dog walking for fitness, along with the boost of ownership itself.

The most common injuries listed in the National Electronic Injury Surveillance System database were finger fracture, traumatic brain injury, and shoulder sprain or strain. These mostly involved falls from being pulled, tripped, or tangled up in the leash while walking. For those aged 65 years and older, traumatic brain injury and hip fracture were the most common.

Women were 50% more likely to sustain a fracture than were men, and dog owners aged 65 and older were three times as likely to fall, twice as likely to get a fracture, and 60% more likely to have brain injury than were younger people. Now, that’s not to say younger people don’t also get hurt. After all, dogs aren’t ageists. The researchers have that data but it’s coming out later.

Meanwhile, the pitfalls involved with just trying to get our daily steps in while letting Muffin do her business have us on the lookout for random squirrels.

Taking a swing against arthritis

Osteoarthritis is a tough disease to manage. Exercise helps ease the stiffness and pain of the joints, but at the same time, the disease makes it difficult to do that beneficial exercise. Even a relatively simple activity like jogging can hurt more than it helps. If only there were a low-impact exercise that was incredibly popular among the generally older population who are likely to have arthritis.

We love a good golf study here at LOTME, and a group of Australian and U.K. researchers have provided. Osteoarthritis affects 2 million people in the land down under, making it the most common source of disability there. In that population, only 64% reported their physical health to be good, very good, or excellent. Among the 459 golfers with OA that the study authors surveyed, however, the percentage reporting good health rose to more than 90%.

jacoblund/Getty Images

A similar story emerged when they looked at mental health. Nearly a quarter of nongolfers with OA reported high or very high levels of psychological distress, compared with just 8% of golfers. This pattern of improved physical and mental health remained when the researchers looked at the general, non-OA population.

This isn’t the first time golf’s been connected with improved health, and previous studies have shown golf to reduce the risks of cardiovascular disease, diabetes, and obesity, among other things. Just walking one 18-hole round significantly exceeds the CDC’s recommended 150 minutes of physical activity per week. Go out multiple times a week – leaving the cart and beer at home, American golfers – and you’ll be fit for a lifetime.

The golfers on our staff, however, are still waiting for those mental health benefits to kick in. Because when we’re adding up our scorecard after that string of four double bogeys to end the round, we’re most definitely thinking: “Yes, this sport is reducing my psychological distress. I am having fun right now.”
 

Battle of the sexes’ intestines

There are, we’re sure you’ve noticed, some differences between males and females. Females, for one thing, have longer small intestines than males. Everybody knows that, right? You didn’t know? Really? … Really?

Afif Ramdhasuma/Unsplash

Well, then, we’re guessing you haven’t read “Hidden diversity: Comparative functional morphology of humans and other species” by Erin A. McKenney, PhD, of North Carolina State University, Raleigh, and associates, which just appeared in PeerJ. We couldn’t put it down, even in the shower – a real page-turner/scroller. (It’s a great way to clean a phone, for those who also like to scroll, text, or talk on the toilet.)

The researchers got out their rulers, calipers, and string and took many measurements of the digestive systems of 45 human cadavers (21 female and 24 male), which were compared with data from 10 rats, 10 pigs, and 10 bullfrogs, which had been collected (the measurements, not the animals) by undergraduate students enrolled in a comparative anatomy laboratory course at the university.

There was little intestinal-length variation among the four-legged subjects, but when it comes to humans, females have “consistently and significantly longer small intestines than males,” the investigators noted.

The women’s small intestines, almost 14 feet long on average, were about a foot longer than the men’s, which suggests that women are better able to extract nutrients from food and “supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” coauthor Amanda Hale said in a written statement from the school. The way to a man’s heart may be through his stomach, but the way to a woman’s heart is through her duodenum, it seems.

Fascinating stuff, to be sure, but the thing that really caught our eye in the PeerJ article was the authors’ suggestion “that organs behave independently of one another, both within and across species.” Organs behaving independently? A somewhat ominous concept, no doubt, but it does explain a lot of the sounds we hear coming from our guts, which can get pretty frightening, especially on chili night.
 

Dog walking is dangerous business

Yes, you did read that right. A lot of strange things can send you to the emergency department. Go ahead and add dog walking onto that list.

Investigators from Johns Hopkins University estimate that over 422,000 adults presented to U.S. emergency departments with leash-dependent dog walking-related injuries between 2001 and 2020.

freestocks/Unsplash

With almost 53% of U.S. households owning at least one dog in 2021-2022 in the wake of the COVID pet boom, this kind of occurrence is becoming more common than you think. The annual number of dog-walking injuries more than quadrupled from 7,300 to 32,000 over the course of the study, and the researchers link that spike to the promotion of dog walking for fitness, along with the boost of ownership itself.

The most common injuries listed in the National Electronic Injury Surveillance System database were finger fracture, traumatic brain injury, and shoulder sprain or strain. These mostly involved falls from being pulled, tripped, or tangled up in the leash while walking. For those aged 65 years and older, traumatic brain injury and hip fracture were the most common.

Women were 50% more likely to sustain a fracture than were men, and dog owners aged 65 and older were three times as likely to fall, twice as likely to get a fracture, and 60% more likely to have brain injury than were younger people. Now, that’s not to say younger people don’t also get hurt. After all, dogs aren’t ageists. The researchers have that data but it’s coming out later.

Meanwhile, the pitfalls involved with just trying to get our daily steps in while letting Muffin do her business have us on the lookout for random squirrels.

Taking a swing against arthritis

Osteoarthritis is a tough disease to manage. Exercise helps ease the stiffness and pain of the joints, but at the same time, the disease makes it difficult to do that beneficial exercise. Even a relatively simple activity like jogging can hurt more than it helps. If only there were a low-impact exercise that was incredibly popular among the generally older population who are likely to have arthritis.

We love a good golf study here at LOTME, and a group of Australian and U.K. researchers have provided. Osteoarthritis affects 2 million people in the land down under, making it the most common source of disability there. In that population, only 64% reported their physical health to be good, very good, or excellent. Among the 459 golfers with OA that the study authors surveyed, however, the percentage reporting good health rose to more than 90%.

jacoblund/Getty Images

A similar story emerged when they looked at mental health. Nearly a quarter of nongolfers with OA reported high or very high levels of psychological distress, compared with just 8% of golfers. This pattern of improved physical and mental health remained when the researchers looked at the general, non-OA population.

This isn’t the first time golf’s been connected with improved health, and previous studies have shown golf to reduce the risks of cardiovascular disease, diabetes, and obesity, among other things. Just walking one 18-hole round significantly exceeds the CDC’s recommended 150 minutes of physical activity per week. Go out multiple times a week – leaving the cart and beer at home, American golfers – and you’ll be fit for a lifetime.

The golfers on our staff, however, are still waiting for those mental health benefits to kick in. Because when we’re adding up our scorecard after that string of four double bogeys to end the round, we’re most definitely thinking: “Yes, this sport is reducing my psychological distress. I am having fun right now.”
 

Battle of the sexes’ intestines

There are, we’re sure you’ve noticed, some differences between males and females. Females, for one thing, have longer small intestines than males. Everybody knows that, right? You didn’t know? Really? … Really?

Afif Ramdhasuma/Unsplash

Well, then, we’re guessing you haven’t read “Hidden diversity: Comparative functional morphology of humans and other species” by Erin A. McKenney, PhD, of North Carolina State University, Raleigh, and associates, which just appeared in PeerJ. We couldn’t put it down, even in the shower – a real page-turner/scroller. (It’s a great way to clean a phone, for those who also like to scroll, text, or talk on the toilet.)

The researchers got out their rulers, calipers, and string and took many measurements of the digestive systems of 45 human cadavers (21 female and 24 male), which were compared with data from 10 rats, 10 pigs, and 10 bullfrogs, which had been collected (the measurements, not the animals) by undergraduate students enrolled in a comparative anatomy laboratory course at the university.

There was little intestinal-length variation among the four-legged subjects, but when it comes to humans, females have “consistently and significantly longer small intestines than males,” the investigators noted.

The women’s small intestines, almost 14 feet long on average, were about a foot longer than the men’s, which suggests that women are better able to extract nutrients from food and “supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” coauthor Amanda Hale said in a written statement from the school. The way to a man’s heart may be through his stomach, but the way to a woman’s heart is through her duodenum, it seems.

Fascinating stuff, to be sure, but the thing that really caught our eye in the PeerJ article was the authors’ suggestion “that organs behave independently of one another, both within and across species.” Organs behaving independently? A somewhat ominous concept, no doubt, but it does explain a lot of the sounds we hear coming from our guts, which can get pretty frightening, especially on chili night.
 

Dog walking is dangerous business

Yes, you did read that right. A lot of strange things can send you to the emergency department. Go ahead and add dog walking onto that list.

Investigators from Johns Hopkins University estimate that over 422,000 adults presented to U.S. emergency departments with leash-dependent dog walking-related injuries between 2001 and 2020.

freestocks/Unsplash

With almost 53% of U.S. households owning at least one dog in 2021-2022 in the wake of the COVID pet boom, this kind of occurrence is becoming more common than you think. The annual number of dog-walking injuries more than quadrupled from 7,300 to 32,000 over the course of the study, and the researchers link that spike to the promotion of dog walking for fitness, along with the boost of ownership itself.

The most common injuries listed in the National Electronic Injury Surveillance System database were finger fracture, traumatic brain injury, and shoulder sprain or strain. These mostly involved falls from being pulled, tripped, or tangled up in the leash while walking. For those aged 65 years and older, traumatic brain injury and hip fracture were the most common.

Women were 50% more likely to sustain a fracture than were men, and dog owners aged 65 and older were three times as likely to fall, twice as likely to get a fracture, and 60% more likely to have brain injury than were younger people. Now, that’s not to say younger people don’t also get hurt. After all, dogs aren’t ageists. The researchers have that data but it’s coming out later.

Meanwhile, the pitfalls involved with just trying to get our daily steps in while letting Muffin do her business have us on the lookout for random squirrels.

PHOENIX – When Kathy Givens walked onstage during a plenary session at the annual conference of the American Society for Laser Medicine and Surgery to reflect on her 9-month ordeal being sex trafficked in Texas more than 20 years ago, you could hear a pin drop.

“One of the scariest things about the life of sex trafficking is not knowing who’s going to be on the other side,” said Ms. Givens, who now lives in Houston. “There was some violence. There were some horrible things that happened. But you know what was really scary? When I got out. People may ask, ‘How’s that so? You escaped your trafficker. The past is behind you. Why were you afraid?’ I was afraid because I didn’t know that I had community. I didn’t know that community or that society would care about someone like me.”

Doug Brunk/MDedge News

She said that she found herself immobilized by fear of being shamed in society and labeled a sex trafficking victim, and wondered if she could overcome that fear and if anyone would view her as human again. Once free from her trafficker, she began a “healing journey,” which included getting married, raising four children, and re-enrolling in college with hopes of becoming a social worker. In 2020, she and her husband founded Twelve 11 Partners, an organization committed to supporting human trafficking survivors.

“I was working in the anti-trafficking field helping other survivors ... who have experienced this horrific crime,” she said. “I thought I was on my way.” But one “stain” from her sex trafficking past remained: The name of her trafficker was tattooed on her skin, “a reminder of what I’d gone through.”

Ms. Givens was eventually introduced to Paul M. Friedman, MD, the current ASLMS president and one of the nearly 90 physicians in the United States and Canada who perform tattoo removal free of charge for trafficking survivors as part of the New Beginnings: Tattoo Removal Program, a partnership between the ASLMS and the National Trafficking Sheltered Alliance (NTSA) that was formed in 2022. According to a survey that Dr. Friedman and colleagues presented at the 2022 annual ASLMS conference, an estimated 1 in 2 sex trafficking survivors have branding tattoos, and at least 1,000 survivors a year could benefit from removal of those tattoos.

“To date, 87 physicians in the U.S. and one in Canada have stepped forward to volunteer their services to be part of this program,” Dr. Friedman, who directs the Dermatology and Laser Surgery Center in Houston, said at this year’s meeting. “My goal is to double this number by the next annual conference,” he added, noting that trauma-informed training is part of the program, “to support the survivor experience during the treatment process.”

ASLMS is also working on this issue in partnership with the American Academy of Dermatology (AAD) Ad Hoc Task Force on Dermatological Resources for the Intervention and Prevention of Human Trafficking, which is headed by Boston dermatologist Shadi Kourosh, MD.

“Dermatologists are uniquely positioned to aid in efforts to assist those experiences in trafficking with our training to recognize and diagnose relevant signs on the skin and to assist patients with certain aspects of care and recovery including the treatment of the disease of scars and tattoos,” Dr. Friedman said. “Ultimately, we hope to create a database together to improve recognition of branding tattoos to aid in identifying sex trafficking victims.”

Ms. Givens, who sits on the U.S. Advisory Council on Human Trafficking, said that she was able to truly close the door on her sex trafficking past thanks to the tattoo removal Dr. Friedman performed as part of New Beginnings. “It means the world to me to know that I can now be an advocate for other individuals who have experienced human trafficking,” she told meeting attendees.

“Again, one of the scariest things is not knowing that you have community. I was scared of losing hope, but I’m standing here today. I have all the hope that I need. You have the power to change lives.”

PHOENIX – When Kathy Givens walked onstage during a plenary session at the annual conference of the American Society for Laser Medicine and Surgery to reflect on her 9-month ordeal being sex trafficked in Texas more than 20 years ago, you could hear a pin drop.

“One of the scariest things about the life of sex trafficking is not knowing who’s going to be on the other side,” said Ms. Givens, who now lives in Houston. “There was some violence. There were some horrible things that happened. But you know what was really scary? When I got out. People may ask, ‘How’s that so? You escaped your trafficker. The past is behind you. Why were you afraid?’ I was afraid because I didn’t know that I had community. I didn’t know that community or that society would care about someone like me.”

Doug Brunk/MDedge News

She said that she found herself immobilized by fear of being shamed in society and labeled a sex trafficking victim, and wondered if she could overcome that fear and if anyone would view her as human again. Once free from her trafficker, she began a “healing journey,” which included getting married, raising four children, and re-enrolling in college with hopes of becoming a social worker. In 2020, she and her husband founded Twelve 11 Partners, an organization committed to supporting human trafficking survivors.

“I was working in the anti-trafficking field helping other survivors ... who have experienced this horrific crime,” she said. “I thought I was on my way.” But one “stain” from her sex trafficking past remained: The name of her trafficker was tattooed on her skin, “a reminder of what I’d gone through.”

Ms. Givens was eventually introduced to Paul M. Friedman, MD, the current ASLMS president and one of the nearly 90 physicians in the United States and Canada who perform tattoo removal free of charge for trafficking survivors as part of the New Beginnings: Tattoo Removal Program, a partnership between the ASLMS and the National Trafficking Sheltered Alliance (NTSA) that was formed in 2022. According to a survey that Dr. Friedman and colleagues presented at the 2022 annual ASLMS conference, an estimated 1 in 2 sex trafficking survivors have branding tattoos, and at least 1,000 survivors a year could benefit from removal of those tattoos.

“To date, 87 physicians in the U.S. and one in Canada have stepped forward to volunteer their services to be part of this program,” Dr. Friedman, who directs the Dermatology and Laser Surgery Center in Houston, said at this year’s meeting. “My goal is to double this number by the next annual conference,” he added, noting that trauma-informed training is part of the program, “to support the survivor experience during the treatment process.”

ASLMS is also working on this issue in partnership with the American Academy of Dermatology (AAD) Ad Hoc Task Force on Dermatological Resources for the Intervention and Prevention of Human Trafficking, which is headed by Boston dermatologist Shadi Kourosh, MD.

“Dermatologists are uniquely positioned to aid in efforts to assist those experiences in trafficking with our training to recognize and diagnose relevant signs on the skin and to assist patients with certain aspects of care and recovery including the treatment of the disease of scars and tattoos,” Dr. Friedman said. “Ultimately, we hope to create a database together to improve recognition of branding tattoos to aid in identifying sex trafficking victims.”

Ms. Givens, who sits on the U.S. Advisory Council on Human Trafficking, said that she was able to truly close the door on her sex trafficking past thanks to the tattoo removal Dr. Friedman performed as part of New Beginnings. “It means the world to me to know that I can now be an advocate for other individuals who have experienced human trafficking,” she told meeting attendees.

“Again, one of the scariest things is not knowing that you have community. I was scared of losing hope, but I’m standing here today. I have all the hope that I need. You have the power to change lives.”

PHOENIX – When Kathy Givens walked onstage during a plenary session at the annual conference of the American Society for Laser Medicine and Surgery to reflect on her 9-month ordeal being sex trafficked in Texas more than 20 years ago, you could hear a pin drop.

“One of the scariest things about the life of sex trafficking is not knowing who’s going to be on the other side,” said Ms. Givens, who now lives in Houston. “There was some violence. There were some horrible things that happened. But you know what was really scary? When I got out. People may ask, ‘How’s that so? You escaped your trafficker. The past is behind you. Why were you afraid?’ I was afraid because I didn’t know that I had community. I didn’t know that community or that society would care about someone like me.”

Doug Brunk/MDedge News

She said that she found herself immobilized by fear of being shamed in society and labeled a sex trafficking victim, and wondered if she could overcome that fear and if anyone would view her as human again. Once free from her trafficker, she began a “healing journey,” which included getting married, raising four children, and re-enrolling in college with hopes of becoming a social worker. In 2020, she and her husband founded Twelve 11 Partners, an organization committed to supporting human trafficking survivors.

“I was working in the anti-trafficking field helping other survivors ... who have experienced this horrific crime,” she said. “I thought I was on my way.” But one “stain” from her sex trafficking past remained: The name of her trafficker was tattooed on her skin, “a reminder of what I’d gone through.”

Ms. Givens was eventually introduced to Paul M. Friedman, MD, the current ASLMS president and one of the nearly 90 physicians in the United States and Canada who perform tattoo removal free of charge for trafficking survivors as part of the New Beginnings: Tattoo Removal Program, a partnership between the ASLMS and the National Trafficking Sheltered Alliance (NTSA) that was formed in 2022. According to a survey that Dr. Friedman and colleagues presented at the 2022 annual ASLMS conference, an estimated 1 in 2 sex trafficking survivors have branding tattoos, and at least 1,000 survivors a year could benefit from removal of those tattoos.

“To date, 87 physicians in the U.S. and one in Canada have stepped forward to volunteer their services to be part of this program,” Dr. Friedman, who directs the Dermatology and Laser Surgery Center in Houston, said at this year’s meeting. “My goal is to double this number by the next annual conference,” he added, noting that trauma-informed training is part of the program, “to support the survivor experience during the treatment process.”

ASLMS is also working on this issue in partnership with the American Academy of Dermatology (AAD) Ad Hoc Task Force on Dermatological Resources for the Intervention and Prevention of Human Trafficking, which is headed by Boston dermatologist Shadi Kourosh, MD.

“Dermatologists are uniquely positioned to aid in efforts to assist those experiences in trafficking with our training to recognize and diagnose relevant signs on the skin and to assist patients with certain aspects of care and recovery including the treatment of the disease of scars and tattoos,” Dr. Friedman said. “Ultimately, we hope to create a database together to improve recognition of branding tattoos to aid in identifying sex trafficking victims.”

Ms. Givens, who sits on the U.S. Advisory Council on Human Trafficking, said that she was able to truly close the door on her sex trafficking past thanks to the tattoo removal Dr. Friedman performed as part of New Beginnings. “It means the world to me to know that I can now be an advocate for other individuals who have experienced human trafficking,” she told meeting attendees.

“Again, one of the scariest things is not knowing that you have community. I was scared of losing hope, but I’m standing here today. I have all the hope that I need. You have the power to change lives.”

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

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

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

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

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

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

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

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

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

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

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

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

PHOENIX – Combining intense pulsed light (IPL) with topical radiofrequency (RF) for dry eye disease related to meibomian gland dysfunction resulted in about a doubling of meibomian gland expression and improved meibum quality in both upper and lower eyelids, results from an ongoing, novel study showed.

Dry eye disease affects a large proportion of people in the United States “and the factors that contribute to that are certainly not going away,” lead study author James G. Chelnis MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where he presented the results during an abstract session. “Prepandemic, we used to have meetings in person; now most are on a computer screen,” a common risk factor for worsening dry eyes, he said. Telltale dry eye symptoms include blurry vision, irritation, and corneal damage – mostly caused by meibomian gland dysfunction – which impacts the quality and quantity of meibum secreted. Common treatments include warm compresses, doxycycline, and artificial tears.

Dr. Chelnis

While some studies have shown IPL is helpful in treating dry eye disease caused by meibomian gland dysfunction, little information is available on its use alone or in combination with topical RF to preserve and improve the function of meibomian glands, said Dr. Chelnis, an ophthalmic plastic surgeon in New York City. “The theory here is that the radiofrequency would be able to vibrate the water molecules inside the meibomian glands, which would allow you to turn over the meibum faster, as well as improve the blink reflex response by building supporting collagen,” he said. “Our novel study explores the ability of this combined modality treatment to improve upon meibomian gland health.”
 

Study design, results

Dr. Chelnis and his colleagues enrolled 11 individuals with a previous diagnosis of dry eye disease and meibomian gland dysfunction with Ocular Surface Disease Index (OSDI) survey scores higher than 23, which indicate at least moderate dry eye symptoms. Inclusion criteria were being 22 years of age or older, signs of meibomian gland dysfunction as detected by biomicroscopy, a modified meibomian gland score over 12 in the lower eyelid of at least one eye, and type I-IV skin.

All patients received four treatments (each 2 weeks apart) of IPL to the lower eyelid, surrounding malar region, and nose, followed by 7 minutes of topical RF treatments at 1 MHz and 4 MHz extending to the inferior, lateral, and superior orbital rim. Evaluation of meibomian gland expression and quality of meibum upon expression was conducted following each treatment session, with a final evaluation 4 weeks after the final treatment session.

Meibum quality was evaluated on a scale of 0-3 representing clear (0), cloudy (1), inspissated (2), and blocked (3) meibum, respectively.

Following treatment, meibomian gland expression and meibum quality improved in all eyelids in all 11 patients. Specifically, in the right eye, the number of upper lid expressible glands increased from an average of 13 to 27.9 and the number of lower lid expressible glands increased from an average of 14.6 to 28.2; and in the left eye, the number of upper lid expressible glands increased from an average of 13.3 to 27.3 and the number of lower lid expressible glands increased from an average of 14.8 to 26.8 (P < .001 for all associations).

The overall percentage improvement in meibomian gland expression in the right eye was 82.7% for the upper lids and 136.6% for the lower lids, and in the left eye, 82.9% for the upper lids, and 112.2% for the lower lids.

When comparing upper against lower lids, meibomian gland expression increased 124.4% and 82.8%, respectively. Meibum quality improved in all four eyelids, although upper eyelids displayed a superior improvement compared with lower eyelids.

“We are finding that combining IPL plus RF produces a more complete and comprehensive improvement in the quality of their meibomian gland health, and as such, their dry eyes,” with “a large decrease in their symptom profile,” he concluded.

More patients to be studied

Dr. Chelnis acknowledged certain limitations of the study, including the small number of patients, but he and his colleagues have added an additional clinical site to expand the sample size. “Larger scale studies are needed to evaluate long-term effectiveness of IPL plus RF as well as a comparison with other treatment options.”

During a question-and-answer session Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, who served as one of the abstract session moderators, asked Dr. Chelnis to comment on what the mechanism of action of the IPL-RF combination in improving meibomian gland health.

“It’s not fully understood, but part of it is improved vascularity at the lid margin,” said Dr. Chelnis, who holds a faculty position in the department of ophthalmology at Icahn School of Medicine at Mount Sinai, New York. “Your ocular surface is sort of like your screen door; it catches everything that’s in the environment. An increase in vascularity and immunologic cytokines occurs in response to that. If you’re looking at the eye with a slit lamp, you can see a lot of vascularity that occurs at the lid margin and crowds the meibomian glands. When you decrease that crowding and immunogenic response, you move towards a normally functioning lid margin.”

Dr. Chelnis disclosed that he is a consultant to or an adviser for Lumenis, Horizon Therapeutics, and Soniquence.

PHOENIX – Combining intense pulsed light (IPL) with topical radiofrequency (RF) for dry eye disease related to meibomian gland dysfunction resulted in about a doubling of meibomian gland expression and improved meibum quality in both upper and lower eyelids, results from an ongoing, novel study showed.

Dry eye disease affects a large proportion of people in the United States “and the factors that contribute to that are certainly not going away,” lead study author James G. Chelnis MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where he presented the results during an abstract session. “Prepandemic, we used to have meetings in person; now most are on a computer screen,” a common risk factor for worsening dry eyes, he said. Telltale dry eye symptoms include blurry vision, irritation, and corneal damage – mostly caused by meibomian gland dysfunction – which impacts the quality and quantity of meibum secreted. Common treatments include warm compresses, doxycycline, and artificial tears.

Dr. Chelnis

While some studies have shown IPL is helpful in treating dry eye disease caused by meibomian gland dysfunction, little information is available on its use alone or in combination with topical RF to preserve and improve the function of meibomian glands, said Dr. Chelnis, an ophthalmic plastic surgeon in New York City. “The theory here is that the radiofrequency would be able to vibrate the water molecules inside the meibomian glands, which would allow you to turn over the meibum faster, as well as improve the blink reflex response by building supporting collagen,” he said. “Our novel study explores the ability of this combined modality treatment to improve upon meibomian gland health.”
 

Study design, results

Dr. Chelnis and his colleagues enrolled 11 individuals with a previous diagnosis of dry eye disease and meibomian gland dysfunction with Ocular Surface Disease Index (OSDI) survey scores higher than 23, which indicate at least moderate dry eye symptoms. Inclusion criteria were being 22 years of age or older, signs of meibomian gland dysfunction as detected by biomicroscopy, a modified meibomian gland score over 12 in the lower eyelid of at least one eye, and type I-IV skin.

All patients received four treatments (each 2 weeks apart) of IPL to the lower eyelid, surrounding malar region, and nose, followed by 7 minutes of topical RF treatments at 1 MHz and 4 MHz extending to the inferior, lateral, and superior orbital rim. Evaluation of meibomian gland expression and quality of meibum upon expression was conducted following each treatment session, with a final evaluation 4 weeks after the final treatment session.

Meibum quality was evaluated on a scale of 0-3 representing clear (0), cloudy (1), inspissated (2), and blocked (3) meibum, respectively.

Following treatment, meibomian gland expression and meibum quality improved in all eyelids in all 11 patients. Specifically, in the right eye, the number of upper lid expressible glands increased from an average of 13 to 27.9 and the number of lower lid expressible glands increased from an average of 14.6 to 28.2; and in the left eye, the number of upper lid expressible glands increased from an average of 13.3 to 27.3 and the number of lower lid expressible glands increased from an average of 14.8 to 26.8 (P < .001 for all associations).

The overall percentage improvement in meibomian gland expression in the right eye was 82.7% for the upper lids and 136.6% for the lower lids, and in the left eye, 82.9% for the upper lids, and 112.2% for the lower lids.

When comparing upper against lower lids, meibomian gland expression increased 124.4% and 82.8%, respectively. Meibum quality improved in all four eyelids, although upper eyelids displayed a superior improvement compared with lower eyelids.

“We are finding that combining IPL plus RF produces a more complete and comprehensive improvement in the quality of their meibomian gland health, and as such, their dry eyes,” with “a large decrease in their symptom profile,” he concluded.

More patients to be studied

Dr. Chelnis acknowledged certain limitations of the study, including the small number of patients, but he and his colleagues have added an additional clinical site to expand the sample size. “Larger scale studies are needed to evaluate long-term effectiveness of IPL plus RF as well as a comparison with other treatment options.”

During a question-and-answer session Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, who served as one of the abstract session moderators, asked Dr. Chelnis to comment on what the mechanism of action of the IPL-RF combination in improving meibomian gland health.

“It’s not fully understood, but part of it is improved vascularity at the lid margin,” said Dr. Chelnis, who holds a faculty position in the department of ophthalmology at Icahn School of Medicine at Mount Sinai, New York. “Your ocular surface is sort of like your screen door; it catches everything that’s in the environment. An increase in vascularity and immunologic cytokines occurs in response to that. If you’re looking at the eye with a slit lamp, you can see a lot of vascularity that occurs at the lid margin and crowds the meibomian glands. When you decrease that crowding and immunogenic response, you move towards a normally functioning lid margin.”

Dr. Chelnis disclosed that he is a consultant to or an adviser for Lumenis, Horizon Therapeutics, and Soniquence.

PHOENIX – Combining intense pulsed light (IPL) with topical radiofrequency (RF) for dry eye disease related to meibomian gland dysfunction resulted in about a doubling of meibomian gland expression and improved meibum quality in both upper and lower eyelids, results from an ongoing, novel study showed.

Dry eye disease affects a large proportion of people in the United States “and the factors that contribute to that are certainly not going away,” lead study author James G. Chelnis MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where he presented the results during an abstract session. “Prepandemic, we used to have meetings in person; now most are on a computer screen,” a common risk factor for worsening dry eyes, he said. Telltale dry eye symptoms include blurry vision, irritation, and corneal damage – mostly caused by meibomian gland dysfunction – which impacts the quality and quantity of meibum secreted. Common treatments include warm compresses, doxycycline, and artificial tears.

Dr. Chelnis

While some studies have shown IPL is helpful in treating dry eye disease caused by meibomian gland dysfunction, little information is available on its use alone or in combination with topical RF to preserve and improve the function of meibomian glands, said Dr. Chelnis, an ophthalmic plastic surgeon in New York City. “The theory here is that the radiofrequency would be able to vibrate the water molecules inside the meibomian glands, which would allow you to turn over the meibum faster, as well as improve the blink reflex response by building supporting collagen,” he said. “Our novel study explores the ability of this combined modality treatment to improve upon meibomian gland health.”
 

Study design, results

Dr. Chelnis and his colleagues enrolled 11 individuals with a previous diagnosis of dry eye disease and meibomian gland dysfunction with Ocular Surface Disease Index (OSDI) survey scores higher than 23, which indicate at least moderate dry eye symptoms. Inclusion criteria were being 22 years of age or older, signs of meibomian gland dysfunction as detected by biomicroscopy, a modified meibomian gland score over 12 in the lower eyelid of at least one eye, and type I-IV skin.

All patients received four treatments (each 2 weeks apart) of IPL to the lower eyelid, surrounding malar region, and nose, followed by 7 minutes of topical RF treatments at 1 MHz and 4 MHz extending to the inferior, lateral, and superior orbital rim. Evaluation of meibomian gland expression and quality of meibum upon expression was conducted following each treatment session, with a final evaluation 4 weeks after the final treatment session.

Meibum quality was evaluated on a scale of 0-3 representing clear (0), cloudy (1), inspissated (2), and blocked (3) meibum, respectively.

Following treatment, meibomian gland expression and meibum quality improved in all eyelids in all 11 patients. Specifically, in the right eye, the number of upper lid expressible glands increased from an average of 13 to 27.9 and the number of lower lid expressible glands increased from an average of 14.6 to 28.2; and in the left eye, the number of upper lid expressible glands increased from an average of 13.3 to 27.3 and the number of lower lid expressible glands increased from an average of 14.8 to 26.8 (P < .001 for all associations).

The overall percentage improvement in meibomian gland expression in the right eye was 82.7% for the upper lids and 136.6% for the lower lids, and in the left eye, 82.9% for the upper lids, and 112.2% for the lower lids.

When comparing upper against lower lids, meibomian gland expression increased 124.4% and 82.8%, respectively. Meibum quality improved in all four eyelids, although upper eyelids displayed a superior improvement compared with lower eyelids.

“We are finding that combining IPL plus RF produces a more complete and comprehensive improvement in the quality of their meibomian gland health, and as such, their dry eyes,” with “a large decrease in their symptom profile,” he concluded.

More patients to be studied

Dr. Chelnis acknowledged certain limitations of the study, including the small number of patients, but he and his colleagues have added an additional clinical site to expand the sample size. “Larger scale studies are needed to evaluate long-term effectiveness of IPL plus RF as well as a comparison with other treatment options.”

During a question-and-answer session Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston, who served as one of the abstract session moderators, asked Dr. Chelnis to comment on what the mechanism of action of the IPL-RF combination in improving meibomian gland health.

“It’s not fully understood, but part of it is improved vascularity at the lid margin,” said Dr. Chelnis, who holds a faculty position in the department of ophthalmology at Icahn School of Medicine at Mount Sinai, New York. “Your ocular surface is sort of like your screen door; it catches everything that’s in the environment. An increase in vascularity and immunologic cytokines occurs in response to that. If you’re looking at the eye with a slit lamp, you can see a lot of vascularity that occurs at the lid margin and crowds the meibomian glands. When you decrease that crowding and immunogenic response, you move towards a normally functioning lid margin.”

Dr. Chelnis disclosed that he is a consultant to or an adviser for Lumenis, Horizon Therapeutics, and Soniquence.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

The Janus kinase (JAK) inhibitor upadacitinib is an effective and well-tolerated treatment option for adolescents with moderate to severe atopic dermatitis (AD), an analysis of three clinical trials reports.

Upadacitinib (Rinvoq) was approved by the Food and Drug Administration for treating adults and pediatric patients 12 years of age and older with refractory, moderate to severe AD, in January 2022. This study analyzed the adolescent data in three double-blind, placebo-controlled phase 3 randomized clinical trials, which included adults and 552 adolescents between 12 and 17 years of age with moderate to severe AD in more than 20 countries in Europe, North and South America, the Middle East, Oceania, and the Asia-Pacific region from July 2018 through December 2020.

In the studies, “treatment of moderate to severe AD in adolescents with upadacitinib was effective and generally well tolerated, with an overall efficacy and safety profile similar to that observed in adults, and patient-reported outcomes indicated an overall better health-related quality of life compared with placebo,” lead study author Amy S. Paller, MD, chair of the department of dermatology and professor of dermatology and pediatrics, at Northwestern University, Chicago, and her colleagues write in JAMA Dermatology.

Adolescents in the three studies – Measure Up 1, Measure Up 2, and AD Up – received once-daily oral upadacitinib 15 mg, 30 mg, or placebo. All participants in AD Up used topical corticosteroids.

At 16 weeks, in Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents improved by at least 75% in the Eczema Area and Severity Index (EASI 75) with upadacitinib 15 mg (73%, 69%, 63%); and with upadacitinib 30 mg (78%, 73%, 84%), compared with placebo (12%, 13%, 30%), (P < .001 for all comparisons vs. placebo).

Upadacitinib was generally well tolerated among the adolescents, with mild or moderate acne being the most common adverse event, reported in 10%-13% of those on 15 mg and 15%-16% of those on 30 mg vs. 2%-3% of those on placebo.

Asked to comment on the study, Peck Ong, MD, a pediatric allergist and immunologist at Children’s Hospital Los Angeles, said that he was not surprised by the drug’s effectiveness because JAK inhibitors are potent immunosuppressants. Strengths of the studies include the many pediatric participants, its international reach, and its use of standardized and validated measures, said Dr. Ong, who was not involved in the study.

“The effect of JAK inhibitors is more specific than traditional immunosuppressants such as cyclosporine and methotrexate but not as specific as biologics; therefore, long-term safety data are needed,” he advised. “16 weeks is a very short time to study a chronic disease like atopic dermatitis. We need safety data longer than 1 year.”

Given the disease’s potential impact on self-esteem, sleep, and other important areas of life, Sean Reynolds, MBBCH, a pediatric dermatologist at Children’s Mercy Kansas City (Mo.), welcomed the data on the newer pharmacologic agents.

“FDA-approved systemic treatment options for adolescents with AD are currently limited, which necessitates studies such as this that explore additional treatment options,” said Dr. Reynolds, who also was not involved in the study, told this news organization.

He added that oral upadacitinib may especially help patients who have not found relief with other topical or systemic treatments or who are needle phobic. While the overall efficacy and relatively mild side effects for most patients taking upadacitinib in the trials are encouraging, “the long-term efficacy and side effects in this population require further study, especially considering the limited systemic AD treatment options available in this age group,” he added.

“Given the reported use of other JAK inhibitors to treat myriad inflammatory skin conditions beyond atopic dermatitis, the potential use of upadacitinib and other JAK inhibitors to treat these skin diseases in children and adolescents represents an exciting area for future study in the field of pediatric dermatology,” Dr. Reynolds noted.

The study was funded by AbbVie, the developer and manufacturer of upadacitinib. Dr. Paller and almost all other authors reported relevant financial relationships with AbbVie and other pharmaceutical companies. Dr. Ong reported serving on an AbbVie advisory board, and Dr. Reynolds reported no conflict of interest with the study.

The Janus kinase (JAK) inhibitor upadacitinib is an effective and well-tolerated treatment option for adolescents with moderate to severe atopic dermatitis (AD), an analysis of three clinical trials reports.

Upadacitinib (Rinvoq) was approved by the Food and Drug Administration for treating adults and pediatric patients 12 years of age and older with refractory, moderate to severe AD, in January 2022. This study analyzed the adolescent data in three double-blind, placebo-controlled phase 3 randomized clinical trials, which included adults and 552 adolescents between 12 and 17 years of age with moderate to severe AD in more than 20 countries in Europe, North and South America, the Middle East, Oceania, and the Asia-Pacific region from July 2018 through December 2020.

In the studies, “treatment of moderate to severe AD in adolescents with upadacitinib was effective and generally well tolerated, with an overall efficacy and safety profile similar to that observed in adults, and patient-reported outcomes indicated an overall better health-related quality of life compared with placebo,” lead study author Amy S. Paller, MD, chair of the department of dermatology and professor of dermatology and pediatrics, at Northwestern University, Chicago, and her colleagues write in JAMA Dermatology.

Adolescents in the three studies – Measure Up 1, Measure Up 2, and AD Up – received once-daily oral upadacitinib 15 mg, 30 mg, or placebo. All participants in AD Up used topical corticosteroids.

At 16 weeks, in Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents improved by at least 75% in the Eczema Area and Severity Index (EASI 75) with upadacitinib 15 mg (73%, 69%, 63%); and with upadacitinib 30 mg (78%, 73%, 84%), compared with placebo (12%, 13%, 30%), (P < .001 for all comparisons vs. placebo).

Upadacitinib was generally well tolerated among the adolescents, with mild or moderate acne being the most common adverse event, reported in 10%-13% of those on 15 mg and 15%-16% of those on 30 mg vs. 2%-3% of those on placebo.

Asked to comment on the study, Peck Ong, MD, a pediatric allergist and immunologist at Children’s Hospital Los Angeles, said that he was not surprised by the drug’s effectiveness because JAK inhibitors are potent immunosuppressants. Strengths of the studies include the many pediatric participants, its international reach, and its use of standardized and validated measures, said Dr. Ong, who was not involved in the study.

“The effect of JAK inhibitors is more specific than traditional immunosuppressants such as cyclosporine and methotrexate but not as specific as biologics; therefore, long-term safety data are needed,” he advised. “16 weeks is a very short time to study a chronic disease like atopic dermatitis. We need safety data longer than 1 year.”

Given the disease’s potential impact on self-esteem, sleep, and other important areas of life, Sean Reynolds, MBBCH, a pediatric dermatologist at Children’s Mercy Kansas City (Mo.), welcomed the data on the newer pharmacologic agents.

“FDA-approved systemic treatment options for adolescents with AD are currently limited, which necessitates studies such as this that explore additional treatment options,” said Dr. Reynolds, who also was not involved in the study, told this news organization.

He added that oral upadacitinib may especially help patients who have not found relief with other topical or systemic treatments or who are needle phobic. While the overall efficacy and relatively mild side effects for most patients taking upadacitinib in the trials are encouraging, “the long-term efficacy and side effects in this population require further study, especially considering the limited systemic AD treatment options available in this age group,” he added.

“Given the reported use of other JAK inhibitors to treat myriad inflammatory skin conditions beyond atopic dermatitis, the potential use of upadacitinib and other JAK inhibitors to treat these skin diseases in children and adolescents represents an exciting area for future study in the field of pediatric dermatology,” Dr. Reynolds noted.

The study was funded by AbbVie, the developer and manufacturer of upadacitinib. Dr. Paller and almost all other authors reported relevant financial relationships with AbbVie and other pharmaceutical companies. Dr. Ong reported serving on an AbbVie advisory board, and Dr. Reynolds reported no conflict of interest with the study.

The Janus kinase (JAK) inhibitor upadacitinib is an effective and well-tolerated treatment option for adolescents with moderate to severe atopic dermatitis (AD), an analysis of three clinical trials reports.

Upadacitinib (Rinvoq) was approved by the Food and Drug Administration for treating adults and pediatric patients 12 years of age and older with refractory, moderate to severe AD, in January 2022. This study analyzed the adolescent data in three double-blind, placebo-controlled phase 3 randomized clinical trials, which included adults and 552 adolescents between 12 and 17 years of age with moderate to severe AD in more than 20 countries in Europe, North and South America, the Middle East, Oceania, and the Asia-Pacific region from July 2018 through December 2020.

In the studies, “treatment of moderate to severe AD in adolescents with upadacitinib was effective and generally well tolerated, with an overall efficacy and safety profile similar to that observed in adults, and patient-reported outcomes indicated an overall better health-related quality of life compared with placebo,” lead study author Amy S. Paller, MD, chair of the department of dermatology and professor of dermatology and pediatrics, at Northwestern University, Chicago, and her colleagues write in JAMA Dermatology.

Adolescents in the three studies – Measure Up 1, Measure Up 2, and AD Up – received once-daily oral upadacitinib 15 mg, 30 mg, or placebo. All participants in AD Up used topical corticosteroids.

At 16 weeks, in Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents improved by at least 75% in the Eczema Area and Severity Index (EASI 75) with upadacitinib 15 mg (73%, 69%, 63%); and with upadacitinib 30 mg (78%, 73%, 84%), compared with placebo (12%, 13%, 30%), (P < .001 for all comparisons vs. placebo).

Upadacitinib was generally well tolerated among the adolescents, with mild or moderate acne being the most common adverse event, reported in 10%-13% of those on 15 mg and 15%-16% of those on 30 mg vs. 2%-3% of those on placebo.

Asked to comment on the study, Peck Ong, MD, a pediatric allergist and immunologist at Children’s Hospital Los Angeles, said that he was not surprised by the drug’s effectiveness because JAK inhibitors are potent immunosuppressants. Strengths of the studies include the many pediatric participants, its international reach, and its use of standardized and validated measures, said Dr. Ong, who was not involved in the study.

“The effect of JAK inhibitors is more specific than traditional immunosuppressants such as cyclosporine and methotrexate but not as specific as biologics; therefore, long-term safety data are needed,” he advised. “16 weeks is a very short time to study a chronic disease like atopic dermatitis. We need safety data longer than 1 year.”

Given the disease’s potential impact on self-esteem, sleep, and other important areas of life, Sean Reynolds, MBBCH, a pediatric dermatologist at Children’s Mercy Kansas City (Mo.), welcomed the data on the newer pharmacologic agents.

“FDA-approved systemic treatment options for adolescents with AD are currently limited, which necessitates studies such as this that explore additional treatment options,” said Dr. Reynolds, who also was not involved in the study, told this news organization.

He added that oral upadacitinib may especially help patients who have not found relief with other topical or systemic treatments or who are needle phobic. While the overall efficacy and relatively mild side effects for most patients taking upadacitinib in the trials are encouraging, “the long-term efficacy and side effects in this population require further study, especially considering the limited systemic AD treatment options available in this age group,” he added.

“Given the reported use of other JAK inhibitors to treat myriad inflammatory skin conditions beyond atopic dermatitis, the potential use of upadacitinib and other JAK inhibitors to treat these skin diseases in children and adolescents represents an exciting area for future study in the field of pediatric dermatology,” Dr. Reynolds noted.

The study was funded by AbbVie, the developer and manufacturer of upadacitinib. Dr. Paller and almost all other authors reported relevant financial relationships with AbbVie and other pharmaceutical companies. Dr. Ong reported serving on an AbbVie advisory board, and Dr. Reynolds reported no conflict of interest with the study.