Conference Coverage

INDIANAPOLIS – Three factors that may encourage trainees to pursue a career in pediatric dermatology include early exposure to the subspecialty during medical school, mentorship by a board-certified pediatric dermatologist at the trainee’s home institution, and increased salary benefits during and after fellowship.

Those are key findings from a survey of current and prior pediatric dermatology fellows, which sought to investigate what factors influence their career decisions.

According to the study’s principal investigator, Lucia Z. Diaz, MD, pediatric dermatology suffers from workforce shortages and geographic maldistribution as a subspecialty in the United States. She also noted that, from 2016 to 2021, 100% of pediatric dermatology applicants matched, yet about 15 of every 31 positions remained unfilled during each of those years. This suggests that there may be a lack of trainee mentorship secondary to a lack of available pediatric dermatologists.

“Somewhere along the way, we lose trainees to general dermatology, or they may go through a pediatric dermatology fellowship but not actually see children upon completion of their training,” Dr. Diaz, chief of pediatric dermatology at the University of Texas at Austin, said in an interview at the annual meeting of the Society for Pediatric Dermatology, where the study was presented during a poster session. “We wanted to find out factors influencing this.”

For the study, Dr. Diaz, Courtney N. Haller, MD, a first-year dermatology resident at the University of Texas at Austin, and their colleagues emailed a 37-item survey to 59 current and prior pediatric dermatology fellows who trained in the United States in the past 4 years (classes of 2019-2022). Current fellows were asked to share their future plans, and past fellows were asked to share details about their current practice situation including practice type (such as academics, private practice, and a mix of adult and pediatrics), and the researchers used descriptive statistics and chi-square analyses to evaluate qualitative data.

Doug Brunk/MDedge News

In all, 41 survey participants gave complete responses, and 3 gave partial responses. Of these, 8 were current fellows, 36 were past fellows, and 38 were female. The researchers found that 67% of survey respondents first became interested in pediatric dermatology in medical school, while the decision to pursue a fellowship occurred then (33%) or during their third year of dermatology residency (33%). Early exposure to pediatric dermatology, from medical school through dermatology PGY-2, was significantly associated with an early decision to pursue a pediatric dermatology career (P = .004).

In addition, respondents at institutions with two or more pediatric dermatology faculty were significantly more likely to cite home institution mentorship as an influencing factor in their career decision (P = .035).

“I thought that the interest in pediatric dermatology would peak early on during dermatology residency, but it primarily happens during medical school,” said Dr. Diaz, who is also associate director of the dermatology residency program at the medical school. “Mentorship and early exposure to pediatric dermatology during medical school are really important.”

The top three factors that discouraged respondents from pursuing a pediatric dermatology fellowship included a lack of salary benefit with additional training (83%), additional time required to complete training (73%), and geographic relocation (20%). After fellowship, 51% of respondents said they plan to or currently work in academic settings, while 88% said they plan to work full time or currently were working full time.

Interestingly, fellows with additional pediatric training such as an internship or residency were not more likely to see a greater percentage of pediatric patients in practice than those without this training (P = .14). The top 3 reasons for not seeing pediatric patients 100% of the clinical time were interest in seeing adult patients (67%), financial factors (56%), and interest in performing more procedures (56%).

In other findings, the top three factors in deciding practice location were proximity to extended family (63%), practice type (59%), and income (51%).

INDIANAPOLIS – Three factors that may encourage trainees to pursue a career in pediatric dermatology include early exposure to the subspecialty during medical school, mentorship by a board-certified pediatric dermatologist at the trainee’s home institution, and increased salary benefits during and after fellowship.

Those are key findings from a survey of current and prior pediatric dermatology fellows, which sought to investigate what factors influence their career decisions.

According to the study’s principal investigator, Lucia Z. Diaz, MD, pediatric dermatology suffers from workforce shortages and geographic maldistribution as a subspecialty in the United States. She also noted that, from 2016 to 2021, 100% of pediatric dermatology applicants matched, yet about 15 of every 31 positions remained unfilled during each of those years. This suggests that there may be a lack of trainee mentorship secondary to a lack of available pediatric dermatologists.

“Somewhere along the way, we lose trainees to general dermatology, or they may go through a pediatric dermatology fellowship but not actually see children upon completion of their training,” Dr. Diaz, chief of pediatric dermatology at the University of Texas at Austin, said in an interview at the annual meeting of the Society for Pediatric Dermatology, where the study was presented during a poster session. “We wanted to find out factors influencing this.”

For the study, Dr. Diaz, Courtney N. Haller, MD, a first-year dermatology resident at the University of Texas at Austin, and their colleagues emailed a 37-item survey to 59 current and prior pediatric dermatology fellows who trained in the United States in the past 4 years (classes of 2019-2022). Current fellows were asked to share their future plans, and past fellows were asked to share details about their current practice situation including practice type (such as academics, private practice, and a mix of adult and pediatrics), and the researchers used descriptive statistics and chi-square analyses to evaluate qualitative data.

Doug Brunk/MDedge News

In all, 41 survey participants gave complete responses, and 3 gave partial responses. Of these, 8 were current fellows, 36 were past fellows, and 38 were female. The researchers found that 67% of survey respondents first became interested in pediatric dermatology in medical school, while the decision to pursue a fellowship occurred then (33%) or during their third year of dermatology residency (33%). Early exposure to pediatric dermatology, from medical school through dermatology PGY-2, was significantly associated with an early decision to pursue a pediatric dermatology career (P = .004).

In addition, respondents at institutions with two or more pediatric dermatology faculty were significantly more likely to cite home institution mentorship as an influencing factor in their career decision (P = .035).

“I thought that the interest in pediatric dermatology would peak early on during dermatology residency, but it primarily happens during medical school,” said Dr. Diaz, who is also associate director of the dermatology residency program at the medical school. “Mentorship and early exposure to pediatric dermatology during medical school are really important.”

The top three factors that discouraged respondents from pursuing a pediatric dermatology fellowship included a lack of salary benefit with additional training (83%), additional time required to complete training (73%), and geographic relocation (20%). After fellowship, 51% of respondents said they plan to or currently work in academic settings, while 88% said they plan to work full time or currently were working full time.

Interestingly, fellows with additional pediatric training such as an internship or residency were not more likely to see a greater percentage of pediatric patients in practice than those without this training (P = .14). The top 3 reasons for not seeing pediatric patients 100% of the clinical time were interest in seeing adult patients (67%), financial factors (56%), and interest in performing more procedures (56%).

In other findings, the top three factors in deciding practice location were proximity to extended family (63%), practice type (59%), and income (51%).

INDIANAPOLIS – Three factors that may encourage trainees to pursue a career in pediatric dermatology include early exposure to the subspecialty during medical school, mentorship by a board-certified pediatric dermatologist at the trainee’s home institution, and increased salary benefits during and after fellowship.

Those are key findings from a survey of current and prior pediatric dermatology fellows, which sought to investigate what factors influence their career decisions.

According to the study’s principal investigator, Lucia Z. Diaz, MD, pediatric dermatology suffers from workforce shortages and geographic maldistribution as a subspecialty in the United States. She also noted that, from 2016 to 2021, 100% of pediatric dermatology applicants matched, yet about 15 of every 31 positions remained unfilled during each of those years. This suggests that there may be a lack of trainee mentorship secondary to a lack of available pediatric dermatologists.

“Somewhere along the way, we lose trainees to general dermatology, or they may go through a pediatric dermatology fellowship but not actually see children upon completion of their training,” Dr. Diaz, chief of pediatric dermatology at the University of Texas at Austin, said in an interview at the annual meeting of the Society for Pediatric Dermatology, where the study was presented during a poster session. “We wanted to find out factors influencing this.”

For the study, Dr. Diaz, Courtney N. Haller, MD, a first-year dermatology resident at the University of Texas at Austin, and their colleagues emailed a 37-item survey to 59 current and prior pediatric dermatology fellows who trained in the United States in the past 4 years (classes of 2019-2022). Current fellows were asked to share their future plans, and past fellows were asked to share details about their current practice situation including practice type (such as academics, private practice, and a mix of adult and pediatrics), and the researchers used descriptive statistics and chi-square analyses to evaluate qualitative data.

Doug Brunk/MDedge News

In all, 41 survey participants gave complete responses, and 3 gave partial responses. Of these, 8 were current fellows, 36 were past fellows, and 38 were female. The researchers found that 67% of survey respondents first became interested in pediatric dermatology in medical school, while the decision to pursue a fellowship occurred then (33%) or during their third year of dermatology residency (33%). Early exposure to pediatric dermatology, from medical school through dermatology PGY-2, was significantly associated with an early decision to pursue a pediatric dermatology career (P = .004).

In addition, respondents at institutions with two or more pediatric dermatology faculty were significantly more likely to cite home institution mentorship as an influencing factor in their career decision (P = .035).

“I thought that the interest in pediatric dermatology would peak early on during dermatology residency, but it primarily happens during medical school,” said Dr. Diaz, who is also associate director of the dermatology residency program at the medical school. “Mentorship and early exposure to pediatric dermatology during medical school are really important.”

The top three factors that discouraged respondents from pursuing a pediatric dermatology fellowship included a lack of salary benefit with additional training (83%), additional time required to complete training (73%), and geographic relocation (20%). After fellowship, 51% of respondents said they plan to or currently work in academic settings, while 88% said they plan to work full time or currently were working full time.

Interestingly, fellows with additional pediatric training such as an internship or residency were not more likely to see a greater percentage of pediatric patients in practice than those without this training (P = .14). The top 3 reasons for not seeing pediatric patients 100% of the clinical time were interest in seeing adult patients (67%), financial factors (56%), and interest in performing more procedures (56%).

In other findings, the top three factors in deciding practice location were proximity to extended family (63%), practice type (59%), and income (51%).

GLASGOW, Scotland – The wound-healing benefits seen with a topical agent containing the bark derivative oleogel-S10 (Filsuvez) for patients with epidermolysis bullosa (EB) continue to accrue with continued use, suggests data from an open-label extension of EASE, the phase 3 safety and efficacy study of the treatment.

Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.

Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.

The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.

In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.

However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.

In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”

Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”

He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”

“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.

Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.

During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.

While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.

To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.

The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).

However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.

Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.

In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.

Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.

Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.

Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.

Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.

Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.

Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.

The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.

The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.

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

GLASGOW, Scotland – The wound-healing benefits seen with a topical agent containing the bark derivative oleogel-S10 (Filsuvez) for patients with epidermolysis bullosa (EB) continue to accrue with continued use, suggests data from an open-label extension of EASE, the phase 3 safety and efficacy study of the treatment.

Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.

Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.

The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.

In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.

However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.

In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”

Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”

He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”

“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.

Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.

During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.

While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.

To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.

The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).

However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.

Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.

In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.

Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.

Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.

Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.

Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.

Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.

Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.

The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.

The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.

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

GLASGOW, Scotland – The wound-healing benefits seen with a topical agent containing the bark derivative oleogel-S10 (Filsuvez) for patients with epidermolysis bullosa (EB) continue to accrue with continued use, suggests data from an open-label extension of EASE, the phase 3 safety and efficacy study of the treatment.

Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.

Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.

The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.

In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.

However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.

In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”

Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”

He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”

“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.

Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.

During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.

While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.

To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.

The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).

However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.

Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.

In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.

Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.

Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.

Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.

Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.

Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.

Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.

The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.

The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.

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

Long thought to be untreatable, KRAS is one of the most difficult to treat oncogenic drivers responsible for approximately 25% of all tumors, including 68% of pancreatic tumors and 20% of all non–small cell lung cancers (NSCLC).

We now have a treatment – sotorasib – for patients with locally advanced or metastatic NSCLC that is driven by a KRAS mutation (G12C). And, now, there is a second treatment – adagrasib – under study, which, according to a presentation recently made at the annual meeting of the American Society of Clinical Oncology, looks promising.

Ras is a membrane-bound regulatory protein (G protein) belonging to the family of guanosine triphosphatases (GTPases). Ras functions as a guanosine diphosphate/triphosphate binary switch by cycling between the active GTP-bound and the inactive GDP-bound states in response to extracellular stimuli. The KRAS (G12C) mutation affects the active form of KRAS and results in abnormally high concentrations of GTP-bound KRAS leading to hyperactivation of downstream oncogenic pathways and uncontrolled cell growth, specifically of ERK and MEK signaling pathways.

At the ASCO annual meeting in June, Spira and colleagues reported the results of cohort A of the KRYSTAL-1 study evaluating adagrasib as second-line therapy patients with advanced solid tumors harboring a KRAS (G12C) mutation. Like sotorasib, adagrasib is a KRAS (G12C) inhibitor that irreversibly and selectively binds KRAS (G12C), locking it in its inactive state. In this study, patients had to have failed first-line chemotherapy and immunotherapy with 43% of lung cancer patients responding. The 12-month overall survival (OS) was 51%, median overall survival was 12.6 and median progression-free survival (PFS) was 6.5 months. Twenty-five patients with KRAS (G12C)–mutant NSCLC and active, untreated central nervous system metastases received adagrasib in a phase 1b cohort. The intracranial overall response rate was 31.6% and median intracranial PFS was 4.2 months. Systemic ORR was 35.0% (7/20), the disease control rate was 80.0% (16/20) and median duration of response was 9.6 months. Based on these data, a phase 3 trial evaluating adagrasib monotherapy versus docetaxel in previously treated patients with KRAS (G12C) mutant NSCLC is ongoing.

The Food and Drug Administration approval of sotorasib in 2021 was, in part, based on the results of a single-arm, phase 2, second-line study of patients who had previously received platinum-based chemotherapy and/or immunotherapy. An ORR rate of 37.1% was reported with a median PFS of 6.8 months and median OS of 12.5 months leading to the FDA approval. Responses were observed across the range of baseline PD-L1 expression levels: 48% of PD-L1 negative, 39% with PD-L1 between 1%-49%, and 22% of patients with a PD-L1 of greater than 50% having a response.

The major toxicities observed in these studies were gastrointestinal (diarrhea, nausea, vomiting) and hepatic (elevated liver enzymes). About 97% of patients on adagrasib experienced any treatment-related adverse events, and 43% experienced a grade 3 or 4 treatment-related adverse event leading to dose reduction in 52% of patients, a dose interruption in 61% of patients, and a 7% discontinuation rate. About 70% of patients treated with sotorasib had a treatment-related adverse event of any grade, and 21% reported grade 3 or 4 treatment-related adverse events.

A subgroup in the KRYSTAL-1 trial reported an intracranial ORR of 32% in patients with active, untreated CNS metastases. Median overall survival has not yet reached concordance between systemic and intracranial disease control was 88%. In addition, preliminary data from two patients with untreated CNS metastases from a phase 1b cohort found cerebrospinal fluid concentrations of adagrasib with a mean ratio of unbound brain-to-plasma concentration of 0.47, which is comparable or exceeds values for known CNS-penetrant tyrosine kinase inhibitors.

Unfortunately, KRAS (G12C) is not the only KRAS mutation out there. There are a myriad of others, such as G12V and G12D. Hopefully, we will be seeing more drugs aimed at this set of important mutations. Another question, of course, is when and if these drugs will move to the first-line setting.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Long thought to be untreatable, KRAS is one of the most difficult to treat oncogenic drivers responsible for approximately 25% of all tumors, including 68% of pancreatic tumors and 20% of all non–small cell lung cancers (NSCLC).

We now have a treatment – sotorasib – for patients with locally advanced or metastatic NSCLC that is driven by a KRAS mutation (G12C). And, now, there is a second treatment – adagrasib – under study, which, according to a presentation recently made at the annual meeting of the American Society of Clinical Oncology, looks promising.

Ras is a membrane-bound regulatory protein (G protein) belonging to the family of guanosine triphosphatases (GTPases). Ras functions as a guanosine diphosphate/triphosphate binary switch by cycling between the active GTP-bound and the inactive GDP-bound states in response to extracellular stimuli. The KRAS (G12C) mutation affects the active form of KRAS and results in abnormally high concentrations of GTP-bound KRAS leading to hyperactivation of downstream oncogenic pathways and uncontrolled cell growth, specifically of ERK and MEK signaling pathways.

At the ASCO annual meeting in June, Spira and colleagues reported the results of cohort A of the KRYSTAL-1 study evaluating adagrasib as second-line therapy patients with advanced solid tumors harboring a KRAS (G12C) mutation. Like sotorasib, adagrasib is a KRAS (G12C) inhibitor that irreversibly and selectively binds KRAS (G12C), locking it in its inactive state. In this study, patients had to have failed first-line chemotherapy and immunotherapy with 43% of lung cancer patients responding. The 12-month overall survival (OS) was 51%, median overall survival was 12.6 and median progression-free survival (PFS) was 6.5 months. Twenty-five patients with KRAS (G12C)–mutant NSCLC and active, untreated central nervous system metastases received adagrasib in a phase 1b cohort. The intracranial overall response rate was 31.6% and median intracranial PFS was 4.2 months. Systemic ORR was 35.0% (7/20), the disease control rate was 80.0% (16/20) and median duration of response was 9.6 months. Based on these data, a phase 3 trial evaluating adagrasib monotherapy versus docetaxel in previously treated patients with KRAS (G12C) mutant NSCLC is ongoing.

The Food and Drug Administration approval of sotorasib in 2021 was, in part, based on the results of a single-arm, phase 2, second-line study of patients who had previously received platinum-based chemotherapy and/or immunotherapy. An ORR rate of 37.1% was reported with a median PFS of 6.8 months and median OS of 12.5 months leading to the FDA approval. Responses were observed across the range of baseline PD-L1 expression levels: 48% of PD-L1 negative, 39% with PD-L1 between 1%-49%, and 22% of patients with a PD-L1 of greater than 50% having a response.

The major toxicities observed in these studies were gastrointestinal (diarrhea, nausea, vomiting) and hepatic (elevated liver enzymes). About 97% of patients on adagrasib experienced any treatment-related adverse events, and 43% experienced a grade 3 or 4 treatment-related adverse event leading to dose reduction in 52% of patients, a dose interruption in 61% of patients, and a 7% discontinuation rate. About 70% of patients treated with sotorasib had a treatment-related adverse event of any grade, and 21% reported grade 3 or 4 treatment-related adverse events.

A subgroup in the KRYSTAL-1 trial reported an intracranial ORR of 32% in patients with active, untreated CNS metastases. Median overall survival has not yet reached concordance between systemic and intracranial disease control was 88%. In addition, preliminary data from two patients with untreated CNS metastases from a phase 1b cohort found cerebrospinal fluid concentrations of adagrasib with a mean ratio of unbound brain-to-plasma concentration of 0.47, which is comparable or exceeds values for known CNS-penetrant tyrosine kinase inhibitors.

Unfortunately, KRAS (G12C) is not the only KRAS mutation out there. There are a myriad of others, such as G12V and G12D. Hopefully, we will be seeing more drugs aimed at this set of important mutations. Another question, of course, is when and if these drugs will move to the first-line setting.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Long thought to be untreatable, KRAS is one of the most difficult to treat oncogenic drivers responsible for approximately 25% of all tumors, including 68% of pancreatic tumors and 20% of all non–small cell lung cancers (NSCLC).

We now have a treatment – sotorasib – for patients with locally advanced or metastatic NSCLC that is driven by a KRAS mutation (G12C). And, now, there is a second treatment – adagrasib – under study, which, according to a presentation recently made at the annual meeting of the American Society of Clinical Oncology, looks promising.

Ras is a membrane-bound regulatory protein (G protein) belonging to the family of guanosine triphosphatases (GTPases). Ras functions as a guanosine diphosphate/triphosphate binary switch by cycling between the active GTP-bound and the inactive GDP-bound states in response to extracellular stimuli. The KRAS (G12C) mutation affects the active form of KRAS and results in abnormally high concentrations of GTP-bound KRAS leading to hyperactivation of downstream oncogenic pathways and uncontrolled cell growth, specifically of ERK and MEK signaling pathways.

At the ASCO annual meeting in June, Spira and colleagues reported the results of cohort A of the KRYSTAL-1 study evaluating adagrasib as second-line therapy patients with advanced solid tumors harboring a KRAS (G12C) mutation. Like sotorasib, adagrasib is a KRAS (G12C) inhibitor that irreversibly and selectively binds KRAS (G12C), locking it in its inactive state. In this study, patients had to have failed first-line chemotherapy and immunotherapy with 43% of lung cancer patients responding. The 12-month overall survival (OS) was 51%, median overall survival was 12.6 and median progression-free survival (PFS) was 6.5 months. Twenty-five patients with KRAS (G12C)–mutant NSCLC and active, untreated central nervous system metastases received adagrasib in a phase 1b cohort. The intracranial overall response rate was 31.6% and median intracranial PFS was 4.2 months. Systemic ORR was 35.0% (7/20), the disease control rate was 80.0% (16/20) and median duration of response was 9.6 months. Based on these data, a phase 3 trial evaluating adagrasib monotherapy versus docetaxel in previously treated patients with KRAS (G12C) mutant NSCLC is ongoing.

The Food and Drug Administration approval of sotorasib in 2021 was, in part, based on the results of a single-arm, phase 2, second-line study of patients who had previously received platinum-based chemotherapy and/or immunotherapy. An ORR rate of 37.1% was reported with a median PFS of 6.8 months and median OS of 12.5 months leading to the FDA approval. Responses were observed across the range of baseline PD-L1 expression levels: 48% of PD-L1 negative, 39% with PD-L1 between 1%-49%, and 22% of patients with a PD-L1 of greater than 50% having a response.

The major toxicities observed in these studies were gastrointestinal (diarrhea, nausea, vomiting) and hepatic (elevated liver enzymes). About 97% of patients on adagrasib experienced any treatment-related adverse events, and 43% experienced a grade 3 or 4 treatment-related adverse event leading to dose reduction in 52% of patients, a dose interruption in 61% of patients, and a 7% discontinuation rate. About 70% of patients treated with sotorasib had a treatment-related adverse event of any grade, and 21% reported grade 3 or 4 treatment-related adverse events.

A subgroup in the KRYSTAL-1 trial reported an intracranial ORR of 32% in patients with active, untreated CNS metastases. Median overall survival has not yet reached concordance between systemic and intracranial disease control was 88%. In addition, preliminary data from two patients with untreated CNS metastases from a phase 1b cohort found cerebrospinal fluid concentrations of adagrasib with a mean ratio of unbound brain-to-plasma concentration of 0.47, which is comparable or exceeds values for known CNS-penetrant tyrosine kinase inhibitors.

Unfortunately, KRAS (G12C) is not the only KRAS mutation out there. There are a myriad of others, such as G12V and G12D. Hopefully, we will be seeing more drugs aimed at this set of important mutations. Another question, of course, is when and if these drugs will move to the first-line setting.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.

Based on biomarker findings, some patients may be able to avoid radiation therapy following breast-conserving surgery, suggest results from the LUMINA trial.

The women in this trial who skipped radiotherapy, and were treated with breast-conserving surgery followed by endocrine therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, which was the study’s primary endpoint.

“Women 55 and over, with low-grade luminal A-type breast cancer, following breast conserving surgery and treated with endocrine therapy alone, had a very low rate of local recurrence at 5 years,” commented lead author Timothy Joseph Whelan, MD.

“The prospective and multicenter nature of this study supports that these patients are candidates for the omission of radiotherapy,” said Dr. Whelan, oncology professor and Canada Research Chair in Breast Cancer Research at McMaster University and a radiation oncologist at the Juravinski Cancer Centre, both in Hamilton, Ont.

“Over 300,000 [people] are diagnosed with invasive breast cancer in North America annually, the majority in the United States,” said Dr. Whelan. “We estimate that these results could apply to 10%-15% of them, so about 30,000-40,000 women per year who could avoid the morbidity, the cost, and inconvenience of radiotherapy.”

The results were presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Whelan explained that adjuvant radiation therapy is generally prescribed following breast conservation therapy to lower the risk of local recurrence, but the treatment is also associated with acute and late toxicity. In addition, it can incur high costs and inconvenience for the patient.

Previous studies have found that among women older than 60 with low-grade, luminal A-type breast cancer who received only breast-conserving surgery, there was a low rate of local recurrence. In women aged older than 70 years, the risk of local recurrence was about 4%-5%.

This latest study focused on patients with breast cancer with a luminal A subtype combined with clinical pathological factors (defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2 negative, and Ki67 ≤ 13.25%).

This was a prospective, multicenter cohort study that included 501 patients aged 55 years and older who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The median patient age was 67, with 442 (88%) older than 75 years. The median tumor size was 1.1 cm.

Median follow-up was 5 years. The cohort was followed every 6 months for the first 2 years and then annually.

The primary outcome was local recurrence defined as time from enrollment to any invasive or noninvasive cancer in the ipsilateral breast, and secondary endpoints included contralateral breast cancer, relapse-free survival based on any recurrence, disease free survival, second cancer or death, and overall survival.

At five years, there were 10 events of local recurrence, for a rate of 2.3%. For secondary outcomes, there were eight events of contralateral breast cancer (1.9%); 12 relapses for a recurrence-free survival rate of 97.3%; 47 disease progression (23 second nonbreast cancers) for a disease-free survival rate of 89.9%; and 13 deaths, including 1 from breast cancer, for an overall survival of 97.2%.
 

Confirms earlier data

Penny R. Anderson, MD, professor in the department of radiation oncology at Fox Chase Cancer Center, Philadelphia, commented that this was an “extremely well-designed and important study.

“It has identified a specific subset of patients to be appropriate candidates for consideration of omission of adjuvant breast radiation therapy after breast-conserving surgery,” she added.

Although previously published trials have helped identify certain patient groups who have a low risk of local recurrence – and therefore, for whom it may be appropriate to omit radiation – they have been based on the traditional clinical and pathologic factors of tumor size, margin status, receptor status, and patient age.

“This LUMINA trial utilizes the molecular-defined intrinsic subtype of luminal A breast cancer to provide additional prognostic information,” she said. “This finding certainly suggests that this group of patients are ideal candidates for the omission of radiation, and that this should be discussed with these patients as a potential option in their treatment management.”

Overall, this trial is a “significant addition and a very relevant contribution to the literature demonstrating that adjuvant breast radiation may safely be omitted in this particular subgroup of breast cancer patients,” she said.
 

Unanswered questions

Commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told this news organization that she thinks the take-home message is that there is “clearly a population of early-stage breast cancer [patients] who after lumpectomy do not benefit from radiation.”

“I think where there will be discussion will be what is the optimal way of identifying that group,” she said, noting that in this study the patients were screened for Ki67, a marker of proliferation. 

Testing for Ki67 is not the standard of care, Dr. Gralow pointed out, and there is also a problem with reproducibility since “every lab does it somewhat differently, because it is not a standard pathology approach.”

There are now many unanswered questions, she noted. “Do we need that central testing of Ki67? Do we need to develop guidelines for how to do this? Is this better than if you’ve already run an Oncotype or a MammaPrint test to see if the patient needs chemo, then would that suffice? That is where the discussion will be. We can reduce the number of patients who need radiation without an increase in local regional recurrence.”

In terms of clinical practice, Dr. Gralow explained that there are already some  data supporting the omission of radiation therapy in an older population with ER-positive small low-grade tumors, and this has become a standard clinical practice. “It’s not based on solid data, but based on an accumulation of retrospective analyses,” she said. “So we have already been doing it for an older population. This would bring down the age group, and it would better define it, and test it prospectively.”
 

Limitations to note

Also commenting on the study, Deborah Axelrod, MD, director of clinical breast surgery at New York University Langone’s Perlmutter Cancer Center, explained that, in the last decade, knowledge about the behavior of breast cancers based on molecular subtyping has greatly increased. “Results of studies such as this have given us information on which cancers need more treatment and for which cancers we can de-escalate treatment,” she said. “Refining this more, it’s about reducing the morbidity and improving quality of life without compromising the oncological outcome.”

She noted that a big strength of this LUMINA study is that it is prospective and multicenter. “It has been supported by other past studies as well and will define for which patients with newly treated breast cancers can we omit radiation, which has been the standard of care,” said Dr. Axelrod. “It is based on the age and biology of breast cancer in defining which patient can forgo radiation and showed a low risk of recurrence in a specific population of women with a favorable breast cancer profile”

There were limitations to the study. “There is a 5-year follow-up and local recurrence for ER-positive cancers continues to rise after 5 years, so longer-term follow-up will be important,” she said. Also, she pointed out that it is a single-arm study so there is no radiation therapy comparison arm.

Other limitations were that the patients were older with smaller tumors, and all were committed to 5 years of endocrine therapy, although compliance with that has not been reported. There may be some older patients who prefer radiation therapy, especially a week of accelerated partial breast irradiation, rather than commit to 5 years of endocrine therapy as mandated in this study.

“Overall, the takeaway message for patients is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” said Dr. Axelrod.

LUMINA was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan has reported research funding from Exact Sciences (Inst). Dr. Axelrod and Dr. Anderson reported no disclosures. Dr. Gralow reported relationships with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen, and Genomic Health.

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

Based on biomarker findings, some patients may be able to avoid radiation therapy following breast-conserving surgery, suggest results from the LUMINA trial.

The women in this trial who skipped radiotherapy, and were treated with breast-conserving surgery followed by endocrine therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, which was the study’s primary endpoint.

“Women 55 and over, with low-grade luminal A-type breast cancer, following breast conserving surgery and treated with endocrine therapy alone, had a very low rate of local recurrence at 5 years,” commented lead author Timothy Joseph Whelan, MD.

“The prospective and multicenter nature of this study supports that these patients are candidates for the omission of radiotherapy,” said Dr. Whelan, oncology professor and Canada Research Chair in Breast Cancer Research at McMaster University and a radiation oncologist at the Juravinski Cancer Centre, both in Hamilton, Ont.

“Over 300,000 [people] are diagnosed with invasive breast cancer in North America annually, the majority in the United States,” said Dr. Whelan. “We estimate that these results could apply to 10%-15% of them, so about 30,000-40,000 women per year who could avoid the morbidity, the cost, and inconvenience of radiotherapy.”

The results were presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Whelan explained that adjuvant radiation therapy is generally prescribed following breast conservation therapy to lower the risk of local recurrence, but the treatment is also associated with acute and late toxicity. In addition, it can incur high costs and inconvenience for the patient.

Previous studies have found that among women older than 60 with low-grade, luminal A-type breast cancer who received only breast-conserving surgery, there was a low rate of local recurrence. In women aged older than 70 years, the risk of local recurrence was about 4%-5%.

This latest study focused on patients with breast cancer with a luminal A subtype combined with clinical pathological factors (defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2 negative, and Ki67 ≤ 13.25%).

This was a prospective, multicenter cohort study that included 501 patients aged 55 years and older who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The median patient age was 67, with 442 (88%) older than 75 years. The median tumor size was 1.1 cm.

Median follow-up was 5 years. The cohort was followed every 6 months for the first 2 years and then annually.

The primary outcome was local recurrence defined as time from enrollment to any invasive or noninvasive cancer in the ipsilateral breast, and secondary endpoints included contralateral breast cancer, relapse-free survival based on any recurrence, disease free survival, second cancer or death, and overall survival.

At five years, there were 10 events of local recurrence, for a rate of 2.3%. For secondary outcomes, there were eight events of contralateral breast cancer (1.9%); 12 relapses for a recurrence-free survival rate of 97.3%; 47 disease progression (23 second nonbreast cancers) for a disease-free survival rate of 89.9%; and 13 deaths, including 1 from breast cancer, for an overall survival of 97.2%.
 

Confirms earlier data

Penny R. Anderson, MD, professor in the department of radiation oncology at Fox Chase Cancer Center, Philadelphia, commented that this was an “extremely well-designed and important study.

“It has identified a specific subset of patients to be appropriate candidates for consideration of omission of adjuvant breast radiation therapy after breast-conserving surgery,” she added.

Although previously published trials have helped identify certain patient groups who have a low risk of local recurrence – and therefore, for whom it may be appropriate to omit radiation – they have been based on the traditional clinical and pathologic factors of tumor size, margin status, receptor status, and patient age.

“This LUMINA trial utilizes the molecular-defined intrinsic subtype of luminal A breast cancer to provide additional prognostic information,” she said. “This finding certainly suggests that this group of patients are ideal candidates for the omission of radiation, and that this should be discussed with these patients as a potential option in their treatment management.”

Overall, this trial is a “significant addition and a very relevant contribution to the literature demonstrating that adjuvant breast radiation may safely be omitted in this particular subgroup of breast cancer patients,” she said.
 

Unanswered questions

Commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told this news organization that she thinks the take-home message is that there is “clearly a population of early-stage breast cancer [patients] who after lumpectomy do not benefit from radiation.”

“I think where there will be discussion will be what is the optimal way of identifying that group,” she said, noting that in this study the patients were screened for Ki67, a marker of proliferation. 

Testing for Ki67 is not the standard of care, Dr. Gralow pointed out, and there is also a problem with reproducibility since “every lab does it somewhat differently, because it is not a standard pathology approach.”

There are now many unanswered questions, she noted. “Do we need that central testing of Ki67? Do we need to develop guidelines for how to do this? Is this better than if you’ve already run an Oncotype or a MammaPrint test to see if the patient needs chemo, then would that suffice? That is where the discussion will be. We can reduce the number of patients who need radiation without an increase in local regional recurrence.”

In terms of clinical practice, Dr. Gralow explained that there are already some  data supporting the omission of radiation therapy in an older population with ER-positive small low-grade tumors, and this has become a standard clinical practice. “It’s not based on solid data, but based on an accumulation of retrospective analyses,” she said. “So we have already been doing it for an older population. This would bring down the age group, and it would better define it, and test it prospectively.”
 

Limitations to note

Also commenting on the study, Deborah Axelrod, MD, director of clinical breast surgery at New York University Langone’s Perlmutter Cancer Center, explained that, in the last decade, knowledge about the behavior of breast cancers based on molecular subtyping has greatly increased. “Results of studies such as this have given us information on which cancers need more treatment and for which cancers we can de-escalate treatment,” she said. “Refining this more, it’s about reducing the morbidity and improving quality of life without compromising the oncological outcome.”

She noted that a big strength of this LUMINA study is that it is prospective and multicenter. “It has been supported by other past studies as well and will define for which patients with newly treated breast cancers can we omit radiation, which has been the standard of care,” said Dr. Axelrod. “It is based on the age and biology of breast cancer in defining which patient can forgo radiation and showed a low risk of recurrence in a specific population of women with a favorable breast cancer profile”

There were limitations to the study. “There is a 5-year follow-up and local recurrence for ER-positive cancers continues to rise after 5 years, so longer-term follow-up will be important,” she said. Also, she pointed out that it is a single-arm study so there is no radiation therapy comparison arm.

Other limitations were that the patients were older with smaller tumors, and all were committed to 5 years of endocrine therapy, although compliance with that has not been reported. There may be some older patients who prefer radiation therapy, especially a week of accelerated partial breast irradiation, rather than commit to 5 years of endocrine therapy as mandated in this study.

“Overall, the takeaway message for patients is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” said Dr. Axelrod.

LUMINA was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan has reported research funding from Exact Sciences (Inst). Dr. Axelrod and Dr. Anderson reported no disclosures. Dr. Gralow reported relationships with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen, and Genomic Health.

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

Based on biomarker findings, some patients may be able to avoid radiation therapy following breast-conserving surgery, suggest results from the LUMINA trial.

The women in this trial who skipped radiotherapy, and were treated with breast-conserving surgery followed by endocrine therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, which was the study’s primary endpoint.

“Women 55 and over, with low-grade luminal A-type breast cancer, following breast conserving surgery and treated with endocrine therapy alone, had a very low rate of local recurrence at 5 years,” commented lead author Timothy Joseph Whelan, MD.

“The prospective and multicenter nature of this study supports that these patients are candidates for the omission of radiotherapy,” said Dr. Whelan, oncology professor and Canada Research Chair in Breast Cancer Research at McMaster University and a radiation oncologist at the Juravinski Cancer Centre, both in Hamilton, Ont.

“Over 300,000 [people] are diagnosed with invasive breast cancer in North America annually, the majority in the United States,” said Dr. Whelan. “We estimate that these results could apply to 10%-15% of them, so about 30,000-40,000 women per year who could avoid the morbidity, the cost, and inconvenience of radiotherapy.”

The results were presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Whelan explained that adjuvant radiation therapy is generally prescribed following breast conservation therapy to lower the risk of local recurrence, but the treatment is also associated with acute and late toxicity. In addition, it can incur high costs and inconvenience for the patient.

Previous studies have found that among women older than 60 with low-grade, luminal A-type breast cancer who received only breast-conserving surgery, there was a low rate of local recurrence. In women aged older than 70 years, the risk of local recurrence was about 4%-5%.

This latest study focused on patients with breast cancer with a luminal A subtype combined with clinical pathological factors (defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2 negative, and Ki67 ≤ 13.25%).

This was a prospective, multicenter cohort study that included 501 patients aged 55 years and older who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The median patient age was 67, with 442 (88%) older than 75 years. The median tumor size was 1.1 cm.

Median follow-up was 5 years. The cohort was followed every 6 months for the first 2 years and then annually.

The primary outcome was local recurrence defined as time from enrollment to any invasive or noninvasive cancer in the ipsilateral breast, and secondary endpoints included contralateral breast cancer, relapse-free survival based on any recurrence, disease free survival, second cancer or death, and overall survival.

At five years, there were 10 events of local recurrence, for a rate of 2.3%. For secondary outcomes, there were eight events of contralateral breast cancer (1.9%); 12 relapses for a recurrence-free survival rate of 97.3%; 47 disease progression (23 second nonbreast cancers) for a disease-free survival rate of 89.9%; and 13 deaths, including 1 from breast cancer, for an overall survival of 97.2%.
 

Confirms earlier data

Penny R. Anderson, MD, professor in the department of radiation oncology at Fox Chase Cancer Center, Philadelphia, commented that this was an “extremely well-designed and important study.

“It has identified a specific subset of patients to be appropriate candidates for consideration of omission of adjuvant breast radiation therapy after breast-conserving surgery,” she added.

Although previously published trials have helped identify certain patient groups who have a low risk of local recurrence – and therefore, for whom it may be appropriate to omit radiation – they have been based on the traditional clinical and pathologic factors of tumor size, margin status, receptor status, and patient age.

“This LUMINA trial utilizes the molecular-defined intrinsic subtype of luminal A breast cancer to provide additional prognostic information,” she said. “This finding certainly suggests that this group of patients are ideal candidates for the omission of radiation, and that this should be discussed with these patients as a potential option in their treatment management.”

Overall, this trial is a “significant addition and a very relevant contribution to the literature demonstrating that adjuvant breast radiation may safely be omitted in this particular subgroup of breast cancer patients,” she said.
 

Unanswered questions

Commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told this news organization that she thinks the take-home message is that there is “clearly a population of early-stage breast cancer [patients] who after lumpectomy do not benefit from radiation.”

“I think where there will be discussion will be what is the optimal way of identifying that group,” she said, noting that in this study the patients were screened for Ki67, a marker of proliferation. 

Testing for Ki67 is not the standard of care, Dr. Gralow pointed out, and there is also a problem with reproducibility since “every lab does it somewhat differently, because it is not a standard pathology approach.”

There are now many unanswered questions, she noted. “Do we need that central testing of Ki67? Do we need to develop guidelines for how to do this? Is this better than if you’ve already run an Oncotype or a MammaPrint test to see if the patient needs chemo, then would that suffice? That is where the discussion will be. We can reduce the number of patients who need radiation without an increase in local regional recurrence.”

In terms of clinical practice, Dr. Gralow explained that there are already some  data supporting the omission of radiation therapy in an older population with ER-positive small low-grade tumors, and this has become a standard clinical practice. “It’s not based on solid data, but based on an accumulation of retrospective analyses,” she said. “So we have already been doing it for an older population. This would bring down the age group, and it would better define it, and test it prospectively.”
 

Limitations to note

Also commenting on the study, Deborah Axelrod, MD, director of clinical breast surgery at New York University Langone’s Perlmutter Cancer Center, explained that, in the last decade, knowledge about the behavior of breast cancers based on molecular subtyping has greatly increased. “Results of studies such as this have given us information on which cancers need more treatment and for which cancers we can de-escalate treatment,” she said. “Refining this more, it’s about reducing the morbidity and improving quality of life without compromising the oncological outcome.”

She noted that a big strength of this LUMINA study is that it is prospective and multicenter. “It has been supported by other past studies as well and will define for which patients with newly treated breast cancers can we omit radiation, which has been the standard of care,” said Dr. Axelrod. “It is based on the age and biology of breast cancer in defining which patient can forgo radiation and showed a low risk of recurrence in a specific population of women with a favorable breast cancer profile”

There were limitations to the study. “There is a 5-year follow-up and local recurrence for ER-positive cancers continues to rise after 5 years, so longer-term follow-up will be important,” she said. Also, she pointed out that it is a single-arm study so there is no radiation therapy comparison arm.

Other limitations were that the patients were older with smaller tumors, and all were committed to 5 years of endocrine therapy, although compliance with that has not been reported. There may be some older patients who prefer radiation therapy, especially a week of accelerated partial breast irradiation, rather than commit to 5 years of endocrine therapy as mandated in this study.

“Overall, the takeaway message for patients is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” said Dr. Axelrod.

LUMINA was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan has reported research funding from Exact Sciences (Inst). Dr. Axelrod and Dr. Anderson reported no disclosures. Dr. Gralow reported relationships with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen, and Genomic Health.

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

INDIANAPOLIS – Infants and preschoolers with atopic dermatitis (AD) experience a substantial disease burden across several domains, including atopic comorbidities, pruritus, sleep loss, hospitalizations, frequent prolonged flares, and school attendance. Those are key findings from a large international web-based survey that was presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

“Improved knowledge of the AD-related burden may help reinforce the medical need in the pediatric population and contribute to better and earlier adequate management of the disease,” authors led by Stephan Weidinger , MD, PhD, vice head of the department of dermatology at University Hospital Schleswig-Holstein, Kiel, Germany, wrote in the abstract.

For the study, Dr. Weidinger and colleagues evaluated 1,486 infants and preschoolers with AD aged 6 months to under 6 years, who participated in the Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE), an international, cross-sectional, web-based survey of children and adolescents. The study population resided in 18 countries from five regions of the world, including North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Parents or guardians answered all questions for infants/preschoolers younger than 4 years of age, while preschoolers aged 4 to younger than 6 years were asked to answer questions related to the impact of AD on their health-related quality of life.

AD severity was assessed using Patient Global Assessment (PtGA), where parents or guardians described their child’s eczema severity over the last week as mild, moderate, or severe. The researchers stratified outcomes by geographic region and AD severity, which included the following atopic comorbidities: worst itch, worst skin pain, and overall sleep disturbance in the past 24 hours as measured by the 0-10 numeric rating scale, where higher scores indicate worse severity; eczema-related hospitalization in the past 12 months; and frequency and average duration of flares over the past month.

The mean age of the study participants was 3 years and 61.6% had mild disease. The most common atopic comorbidities were hay fever, asthma, and seasonal allergies, and the incidence of atopic comorbidities increased with increasing AD severity. One or more atopic comorbidities was reported in 88.3% of patients with mild AD, compared with 92.1% of those with moderate disease and 95.8% of those with severe disease. In addition, infants and preschoolers with moderate or severe AD had worse itch, skin pain, and sleep disturbances over the past 24 hours, compared with those who had mild AD.

More than half of infants and preschoolers with severe AD (54.1%) were reported to have been hospitalized in the past 12 months (this ranged from 30.2% to 71.3% across regions), as did 35% of patients with moderate AD and 32.1% of those with mild AD. In addition, 50.6% of infants and preschoolers with severe AD had more than two flares in the past month, compared with 18.1% of those with moderate AD and 6.3% of those with mild disease.

In other findings, 50.7% of infants and preschoolers with severe AD had flares than lasted an average of 2 or more weeks, compared with 20.8% of those with moderate disease and 10% of those with mild disease. Also, 78.3% of preschoolers aged 4 to less than 6 years had missed one or more days of school in the previous 4 weeks: a mean of 5.1 days among those with mild AD, a mean of 7.3 days among those with moderate AD, and a mean of 12.1 days among those with severe disease.

Raj J. Chovatiya MD, PhD, of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that infants and preschoolers remain an understudied group despite the high prevalence of AD in this age range. “The results of this study demonstrate a substantial burden of disease in this population, particularly among those with more severe disease,” said Dr. Chovatiya, who also directs the university’s Center for Eczema and Itch. “This includes longer and more frequent AD flares as well as high rates of inpatient hospitalization. These findings suggest that additional research is needed to better characterize disease burden and optimize outcomes for young children with AD.”

The study was funded by Regeneron Pharmaceuticals and Sanofi. Dr. Weidinger and other coauthors reported having received institutional research grants and consulting fees from many pharmaceutical companies that manufacture drugs used for the treatment of psoriasis and eczema.

Dr. Chovatiya disclosed that he has served as an advisory board member, consultant, speaker, and/or investigator for AbbVie, Arcutis, Arena, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly, EPI Health, Incyte, L’Oréal, the National Eczema Association, Pfizer, Regeneron, Sanofi, and UCB.

INDIANAPOLIS – Infants and preschoolers with atopic dermatitis (AD) experience a substantial disease burden across several domains, including atopic comorbidities, pruritus, sleep loss, hospitalizations, frequent prolonged flares, and school attendance. Those are key findings from a large international web-based survey that was presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

“Improved knowledge of the AD-related burden may help reinforce the medical need in the pediatric population and contribute to better and earlier adequate management of the disease,” authors led by Stephan Weidinger , MD, PhD, vice head of the department of dermatology at University Hospital Schleswig-Holstein, Kiel, Germany, wrote in the abstract.

For the study, Dr. Weidinger and colleagues evaluated 1,486 infants and preschoolers with AD aged 6 months to under 6 years, who participated in the Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE), an international, cross-sectional, web-based survey of children and adolescents. The study population resided in 18 countries from five regions of the world, including North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Parents or guardians answered all questions for infants/preschoolers younger than 4 years of age, while preschoolers aged 4 to younger than 6 years were asked to answer questions related to the impact of AD on their health-related quality of life.

AD severity was assessed using Patient Global Assessment (PtGA), where parents or guardians described their child’s eczema severity over the last week as mild, moderate, or severe. The researchers stratified outcomes by geographic region and AD severity, which included the following atopic comorbidities: worst itch, worst skin pain, and overall sleep disturbance in the past 24 hours as measured by the 0-10 numeric rating scale, where higher scores indicate worse severity; eczema-related hospitalization in the past 12 months; and frequency and average duration of flares over the past month.

The mean age of the study participants was 3 years and 61.6% had mild disease. The most common atopic comorbidities were hay fever, asthma, and seasonal allergies, and the incidence of atopic comorbidities increased with increasing AD severity. One or more atopic comorbidities was reported in 88.3% of patients with mild AD, compared with 92.1% of those with moderate disease and 95.8% of those with severe disease. In addition, infants and preschoolers with moderate or severe AD had worse itch, skin pain, and sleep disturbances over the past 24 hours, compared with those who had mild AD.

More than half of infants and preschoolers with severe AD (54.1%) were reported to have been hospitalized in the past 12 months (this ranged from 30.2% to 71.3% across regions), as did 35% of patients with moderate AD and 32.1% of those with mild AD. In addition, 50.6% of infants and preschoolers with severe AD had more than two flares in the past month, compared with 18.1% of those with moderate AD and 6.3% of those with mild disease.

In other findings, 50.7% of infants and preschoolers with severe AD had flares than lasted an average of 2 or more weeks, compared with 20.8% of those with moderate disease and 10% of those with mild disease. Also, 78.3% of preschoolers aged 4 to less than 6 years had missed one or more days of school in the previous 4 weeks: a mean of 5.1 days among those with mild AD, a mean of 7.3 days among those with moderate AD, and a mean of 12.1 days among those with severe disease.

Raj J. Chovatiya MD, PhD, of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that infants and preschoolers remain an understudied group despite the high prevalence of AD in this age range. “The results of this study demonstrate a substantial burden of disease in this population, particularly among those with more severe disease,” said Dr. Chovatiya, who also directs the university’s Center for Eczema and Itch. “This includes longer and more frequent AD flares as well as high rates of inpatient hospitalization. These findings suggest that additional research is needed to better characterize disease burden and optimize outcomes for young children with AD.”

The study was funded by Regeneron Pharmaceuticals and Sanofi. Dr. Weidinger and other coauthors reported having received institutional research grants and consulting fees from many pharmaceutical companies that manufacture drugs used for the treatment of psoriasis and eczema.

Dr. Chovatiya disclosed that he has served as an advisory board member, consultant, speaker, and/or investigator for AbbVie, Arcutis, Arena, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly, EPI Health, Incyte, L’Oréal, the National Eczema Association, Pfizer, Regeneron, Sanofi, and UCB.

INDIANAPOLIS – Infants and preschoolers with atopic dermatitis (AD) experience a substantial disease burden across several domains, including atopic comorbidities, pruritus, sleep loss, hospitalizations, frequent prolonged flares, and school attendance. Those are key findings from a large international web-based survey that was presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

“Improved knowledge of the AD-related burden may help reinforce the medical need in the pediatric population and contribute to better and earlier adequate management of the disease,” authors led by Stephan Weidinger , MD, PhD, vice head of the department of dermatology at University Hospital Schleswig-Holstein, Kiel, Germany, wrote in the abstract.

For the study, Dr. Weidinger and colleagues evaluated 1,486 infants and preschoolers with AD aged 6 months to under 6 years, who participated in the Epidemiology of Children with Atopic Dermatitis Reporting on their Experience (EPI-CARE), an international, cross-sectional, web-based survey of children and adolescents. The study population resided in 18 countries from five regions of the world, including North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Parents or guardians answered all questions for infants/preschoolers younger than 4 years of age, while preschoolers aged 4 to younger than 6 years were asked to answer questions related to the impact of AD on their health-related quality of life.

AD severity was assessed using Patient Global Assessment (PtGA), where parents or guardians described their child’s eczema severity over the last week as mild, moderate, or severe. The researchers stratified outcomes by geographic region and AD severity, which included the following atopic comorbidities: worst itch, worst skin pain, and overall sleep disturbance in the past 24 hours as measured by the 0-10 numeric rating scale, where higher scores indicate worse severity; eczema-related hospitalization in the past 12 months; and frequency and average duration of flares over the past month.

The mean age of the study participants was 3 years and 61.6% had mild disease. The most common atopic comorbidities were hay fever, asthma, and seasonal allergies, and the incidence of atopic comorbidities increased with increasing AD severity. One or more atopic comorbidities was reported in 88.3% of patients with mild AD, compared with 92.1% of those with moderate disease and 95.8% of those with severe disease. In addition, infants and preschoolers with moderate or severe AD had worse itch, skin pain, and sleep disturbances over the past 24 hours, compared with those who had mild AD.

More than half of infants and preschoolers with severe AD (54.1%) were reported to have been hospitalized in the past 12 months (this ranged from 30.2% to 71.3% across regions), as did 35% of patients with moderate AD and 32.1% of those with mild AD. In addition, 50.6% of infants and preschoolers with severe AD had more than two flares in the past month, compared with 18.1% of those with moderate AD and 6.3% of those with mild disease.

In other findings, 50.7% of infants and preschoolers with severe AD had flares than lasted an average of 2 or more weeks, compared with 20.8% of those with moderate disease and 10% of those with mild disease. Also, 78.3% of preschoolers aged 4 to less than 6 years had missed one or more days of school in the previous 4 weeks: a mean of 5.1 days among those with mild AD, a mean of 7.3 days among those with moderate AD, and a mean of 12.1 days among those with severe disease.

Raj J. Chovatiya MD, PhD, of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that infants and preschoolers remain an understudied group despite the high prevalence of AD in this age range. “The results of this study demonstrate a substantial burden of disease in this population, particularly among those with more severe disease,” said Dr. Chovatiya, who also directs the university’s Center for Eczema and Itch. “This includes longer and more frequent AD flares as well as high rates of inpatient hospitalization. These findings suggest that additional research is needed to better characterize disease burden and optimize outcomes for young children with AD.”

The study was funded by Regeneron Pharmaceuticals and Sanofi. Dr. Weidinger and other coauthors reported having received institutional research grants and consulting fees from many pharmaceutical companies that manufacture drugs used for the treatment of psoriasis and eczema.

Dr. Chovatiya disclosed that he has served as an advisory board member, consultant, speaker, and/or investigator for AbbVie, Arcutis, Arena, Beiersdorf, Bristol Myers Squibb, Dermavant, Eli Lilly, EPI Health, Incyte, L’Oréal, the National Eczema Association, Pfizer, Regeneron, Sanofi, and UCB.

GLASGOW, Scotland – There are wide variations across Europe in how the different forms of phototherapy are used in the treatment of atopic eczema for both adults and children, reveals a region-wide survey, which points to the need for management guidelines.

Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.

There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.

These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”

Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.

Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”

Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”

“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”

The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”

Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.

Electronic survey

In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.

An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).

The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.

When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.

NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.

For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
 

Frequency of treatment

NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.

The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.

For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.

Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.

The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
 

Use of PUVA, UVA1

The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.

Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.

Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.

But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.

Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

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

GLASGOW, Scotland – There are wide variations across Europe in how the different forms of phototherapy are used in the treatment of atopic eczema for both adults and children, reveals a region-wide survey, which points to the need for management guidelines.

Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.

There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.

These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”

Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.

Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”

Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”

“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”

The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”

Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.

Electronic survey

In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.

An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).

The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.

When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.

NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.

For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
 

Frequency of treatment

NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.

The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.

For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.

Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.

The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
 

Use of PUVA, UVA1

The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.

Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.

Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.

But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.

Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

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

GLASGOW, Scotland – There are wide variations across Europe in how the different forms of phototherapy are used in the treatment of atopic eczema for both adults and children, reveals a region-wide survey, which points to the need for management guidelines.

Over 140 phototherapy practitioners from 27 European countries responded to the survey. Of the practitioners surveyed, 96% used narrow-band ultraviolet B (NB-UVB), and about 50% prescribed psoralen and ultraviolet A (PUVA) for adults. Fewer than 10% did so for children.

There was considerable variation in prescribing practices, “especially when it comes to dosing and treatment duration,” said study presenter Mia Steyn, MD, dermatology registrar, St. John’s Institute of Dermatology, Guy’s and St. Thomas’s Hospital, London.

These results, she said, demonstrate that “an optimal treatment modality either is not known or agreed upon” and that studies are required to determine treatment efficacy, cost, and safety “in a range of skin types.”

Dr. Steyn said that what is needed first is a set of consensus treatment guidelines, “hopefully leading to a randomized controlled trial” that would compare the various treatment options.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 7.

Session co-chair Adam Fityan, MD, a consultant dermatologist at University Hospital Southampton NHS Foundation Trust, U.K., commented that the study was “fascinating” and “really helpful.”

Dr. Fityan, who was not involved with the survey, told this news organization that, “clearly, what we’ve seen is that there is a huge variation in the way everyone uses the different modalities of phototherapy.”

“Having that sort of knowledge will hopefully help us to think a bit more clearly about the regimens and protocols that we use and to maybe find the evidence that everyone needs to have the most effective protocol.”

The data from the study are also useful on an individual level, Dr. Fityan continued, as “you have no idea what anyone is doing” and whether “you are an outlier.”

Dr. Steyn said that phototherapy is commonly used for the treatment of atopic eczema, but the evidence for its efficacy, its impact on quality on life, its cost-effectiveness, and short- and long-term safety is “weak,” particularly in relation to real-life use.

Electronic survey

In lieu of a well-designed randomized controlled trial to answer these questions, the researchers set up a task force to assess how phototherapy is currently being used to treat atopic eczema across the United Kingdom and Europe so as to guide further research.

An electronic survey was devised, and 144 members of phototherapy groups from 27 European countries submitted their responses during 2020. Most responses came from the Netherlands (20), Italy (16), the United Kingdom (14), France (11), and Germany (10).

The results showed that NB-UVB was the most widely used modality of phototherapy, chosen by 96% of respondents. In addition, 17% of respondents said they also prescribed home-based NB-UVB, which was available in eight of the 27 countries.

When asked how they used NB-UVB, the majority (68%) of respondents said they had an age cutoff for use in children, which was set at an average age of 9 years and older, although the range was age 2 years to 16 years.

NBUVB was used as a second-line therapy instead of systemic treatments in up to 93% of adults and in 69% of children. It was used concomitantly with systemic treatment in up to 58% of adults and 11% of children, according to the survey responses.

For about 70% of respondents, the use of NB-UVB was determined by assessing the Fitzpatrick skin type, although almost 40% relied on clinical experience.
 

Frequency of treatment

NB-UVB was prescribed three times a week by 59% of respondents; 31% of respondents prescribed it twice a week; 7%, five times per week; and 2%, four times a week. The typical number of treatments was 21-30 for 53% of respondents, 0-20 treatments for 24%, and 31-40 treatments for 20%.

The dose was typically increased in 10% increments, although there were wide variations in how the treatment was stepped up. Dose was increased after each treatment by almost 50% of respondents, after every two treatments by almost 25%, and after every three treatments by approximately 15%.

For the majority (53%) of respondents, response to NBUVB was assessed after 7-15 treatments, while 43% waited until after 16-30 treatments. Success was defined as a 75% reduction in eczema from baseline by 56% of respondents, while 54% looked to patient satisfaction, and 47% relied on quality of life to determine success of treatment.

Maintenance NB-UVB was never used by 54% of respondents, but 44% said they used it occasionally, and 83% said they did not follow a weaning schedule at the end of treatment.

The most commonly reported adverse effects of NB-UVB were significant erythema, hyperpigmentation, and eczema flare, while the most commonly cited absolute contraindications included a history of melanoma, a history of squamous cell carcinoma, the use of photosensitizing medications, and claustrophobia.
 

Use of PUVA, UVA1

The next most commonly used phototherapy for atopic eczema was PUVA. Although it was available to 83% of respondents, only 52% of respondents had personally prescribed the treatment for adults, and only 7% prescribed it for children.

Of the respondents, 71% said they would switch from NB-UVB to PUVA if desired treatment outcomes were not achieved with the former, and 44% said they would “sometimes consider” PUVA as second-line therapy instead of systemic treatments. Only 13% said they would use it concomitantly with systemic treatment.

Ultraviolet A1 (UVA1) phototherapy was not widely available, with 66% of respondents declaring that they did not have access to this option and just 29% saying they prescribed it.

But when it was used, UVA1 was cited as being used often in adults by 24% of respondents, while 33% used it was used sometimes, and 43% said it was used rarely. It was used for children by 26% of respondents. In addition, 29% said they favored using UVA1 for chronic atopic eczema, and 33% favored using it for acute eczema while 38% had no preference over whether to use it for chronic versus acute atopic eczema.

Similarly to NB-UVB, there were wide variations in the use of PUVA and UVA1 by respondents in terms of dosing schedules, duration of treatment, and how response to treatment was measured.

No funding for the study has been reported. The authors have disclosed no relevant financial relationships.

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

Cognitive impairment is a good predictor of physical disability progression in patients with multiple sclerosis (MS), new research suggests. In an analysis of more than 1,600 patients with secondary-progressive MS (SPMS), the likelihood of needing a wheelchair was almost doubled in those who had the worst scores on cognitive testing measures, compared with their counterparts who had the best scores.

“These findings should change our world view of MS,” study investigator Gavin Giovannoni, PhD, professor of neurology, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, told attendees at the Congress of the European Academy of Neurology.

Expand data

Cognitive impairment occurs very early in the course of MS and is part of the disease, although to a greater or lesser degree depending on the patient, Dr. Giovannoni noted. Such impairment has a significant impact on quality of life for patients dealing with this disease, he added.

EXPAND was a phase 3 study of siponimod. Results showed the now-approved oral selective sphingosine 1–phosphate receptor modulator significantly reduced the risk for disability progression in patients with SPMS.

Using the EXPAND clinical trial database, the current researchers assessed 1,628 participants for an association between cognitive processing speed, as measured with the Symbol Digit Modality Test (SDMT), and physical disability progression, as measured with the Expanded Disability Status Scale (EDSS). A score of 7 or more on the EDSS indicates wheelchair dependence.

Dr. Giovannoni noted that cognitive processing speed is considered an indirect measure of thalamic network efficiency and functional brain reserve.

Investigators looked at both the core study, in which all patients continued on treatment or placebo for up to 37 months, and the core plus extension part, in which patients received treatment for up to 5 years.

They separated SDMT scores into quartiles: from worst (n = 435) to two intermediate quartiles (n = 808) to the best quartile (n = 385).
 

Wheelchair dependence

In addition, the researchers examined the predictive value by baseline SDMT, adjusting for treatment, age, gender, baseline EDSS score, baseline SCMT quartile, and treatment-by-baseline SCMT quartile interaction. On-study SDMT change (month 0-24) was also assessed after adjusting for treatment, age, gender, baseline EDS, baseline SCMT, and on-study change in SCMT quartile.

In the core study, those in the worst SDMT quartile at baseline were numerically more likely to reach deterioration to EDSS 7 or greater (wheelchair dependent), compared with patients in the best SDMT quartile (hazard ratio, 1.31; 95% confidence interval, .72-2.38; P = .371).

The short-term predictive value of baseline SDMT for reaching sustained EDSS of at least 7 was more obvious in the placebo arm than in the treatment arm.

Dr. Giovannoni said this is likely due to the treatment effect of siponimod preventing relatively more events in the worse quartile, and so reducing the risk for wheelchair dependency.

In the core plus extension part, there was an almost twofold increased risk for wheelchair dependence in the worse versus best SDMT groups (HR, 1.81; 95% CI, 1.17-2.78; P = .007).

Both baseline SDMT (HR, 1.81; P = .007) and on-study change in SDMT (HR, 1.73; P = .046) predicted wheelchair dependence in the long-term.
 

‘More important than a walking stick’

Measuring cognitive change over time “may be a more important predictor than a walking stick in terms of quality of life and outcomes, and it affects clinical decisionmaking,” said Dr. Giovannoni.

The findings are not novel, as post hoc analyses of other studies showed similar results. However, this new analysis adds more evidence to the importance of cognition in MS, Dr. Giovannoni noted.

“I have patients with EDSS of 0 or 1 who are profoundly disabled because of cognition. You shouldn’t just assume someone is not disabled because they don’t have physical disability,” he said.

However, Dr. Giovannoni noted that the study found an association and does not necessarily indicate a cause.
 

‘Valuable’ insights

Antonia Lefter, MD, of NeuroHope, Monza Oncologic Hospital, Bucharest, Romania, cochaired the session highlighting the research. Commenting on the study, she called this analysis from the “renowned” EXPAND study “valuable.”

In addition, it “underscores” the importance of assessing cognitive processing speed, as it may predict long-term disability progression in patients with SPMS, Dr. Lefter said.

The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Giovannoni, a steering committee member of the EXPAND trial, reported receiving consulting fees from AbbVie, Actelion, Atara Bio, Biogen, Celgene, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Merck-Serono, Novartis, Roche, and Reva. He has also received compensation for research from Biogen, Roche, Merck-Serono, Novartis, Sanofi-Genzyme, and Takeda. Dr. Lefter has reported no relevant financial relationships.

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

Cognitive impairment is a good predictor of physical disability progression in patients with multiple sclerosis (MS), new research suggests. In an analysis of more than 1,600 patients with secondary-progressive MS (SPMS), the likelihood of needing a wheelchair was almost doubled in those who had the worst scores on cognitive testing measures, compared with their counterparts who had the best scores.

“These findings should change our world view of MS,” study investigator Gavin Giovannoni, PhD, professor of neurology, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, told attendees at the Congress of the European Academy of Neurology.

Expand data

Cognitive impairment occurs very early in the course of MS and is part of the disease, although to a greater or lesser degree depending on the patient, Dr. Giovannoni noted. Such impairment has a significant impact on quality of life for patients dealing with this disease, he added.

EXPAND was a phase 3 study of siponimod. Results showed the now-approved oral selective sphingosine 1–phosphate receptor modulator significantly reduced the risk for disability progression in patients with SPMS.

Using the EXPAND clinical trial database, the current researchers assessed 1,628 participants for an association between cognitive processing speed, as measured with the Symbol Digit Modality Test (SDMT), and physical disability progression, as measured with the Expanded Disability Status Scale (EDSS). A score of 7 or more on the EDSS indicates wheelchair dependence.

Dr. Giovannoni noted that cognitive processing speed is considered an indirect measure of thalamic network efficiency and functional brain reserve.

Investigators looked at both the core study, in which all patients continued on treatment or placebo for up to 37 months, and the core plus extension part, in which patients received treatment for up to 5 years.

They separated SDMT scores into quartiles: from worst (n = 435) to two intermediate quartiles (n = 808) to the best quartile (n = 385).
 

Wheelchair dependence

In addition, the researchers examined the predictive value by baseline SDMT, adjusting for treatment, age, gender, baseline EDSS score, baseline SCMT quartile, and treatment-by-baseline SCMT quartile interaction. On-study SDMT change (month 0-24) was also assessed after adjusting for treatment, age, gender, baseline EDS, baseline SCMT, and on-study change in SCMT quartile.

In the core study, those in the worst SDMT quartile at baseline were numerically more likely to reach deterioration to EDSS 7 or greater (wheelchair dependent), compared with patients in the best SDMT quartile (hazard ratio, 1.31; 95% confidence interval, .72-2.38; P = .371).

The short-term predictive value of baseline SDMT for reaching sustained EDSS of at least 7 was more obvious in the placebo arm than in the treatment arm.

Dr. Giovannoni said this is likely due to the treatment effect of siponimod preventing relatively more events in the worse quartile, and so reducing the risk for wheelchair dependency.

In the core plus extension part, there was an almost twofold increased risk for wheelchair dependence in the worse versus best SDMT groups (HR, 1.81; 95% CI, 1.17-2.78; P = .007).

Both baseline SDMT (HR, 1.81; P = .007) and on-study change in SDMT (HR, 1.73; P = .046) predicted wheelchair dependence in the long-term.
 

‘More important than a walking stick’

Measuring cognitive change over time “may be a more important predictor than a walking stick in terms of quality of life and outcomes, and it affects clinical decisionmaking,” said Dr. Giovannoni.

The findings are not novel, as post hoc analyses of other studies showed similar results. However, this new analysis adds more evidence to the importance of cognition in MS, Dr. Giovannoni noted.

“I have patients with EDSS of 0 or 1 who are profoundly disabled because of cognition. You shouldn’t just assume someone is not disabled because they don’t have physical disability,” he said.

However, Dr. Giovannoni noted that the study found an association and does not necessarily indicate a cause.
 

‘Valuable’ insights

Antonia Lefter, MD, of NeuroHope, Monza Oncologic Hospital, Bucharest, Romania, cochaired the session highlighting the research. Commenting on the study, she called this analysis from the “renowned” EXPAND study “valuable.”

In addition, it “underscores” the importance of assessing cognitive processing speed, as it may predict long-term disability progression in patients with SPMS, Dr. Lefter said.

The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Giovannoni, a steering committee member of the EXPAND trial, reported receiving consulting fees from AbbVie, Actelion, Atara Bio, Biogen, Celgene, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Merck-Serono, Novartis, Roche, and Reva. He has also received compensation for research from Biogen, Roche, Merck-Serono, Novartis, Sanofi-Genzyme, and Takeda. Dr. Lefter has reported no relevant financial relationships.

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

Cognitive impairment is a good predictor of physical disability progression in patients with multiple sclerosis (MS), new research suggests. In an analysis of more than 1,600 patients with secondary-progressive MS (SPMS), the likelihood of needing a wheelchair was almost doubled in those who had the worst scores on cognitive testing measures, compared with their counterparts who had the best scores.

“These findings should change our world view of MS,” study investigator Gavin Giovannoni, PhD, professor of neurology, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, told attendees at the Congress of the European Academy of Neurology.

Expand data

Cognitive impairment occurs very early in the course of MS and is part of the disease, although to a greater or lesser degree depending on the patient, Dr. Giovannoni noted. Such impairment has a significant impact on quality of life for patients dealing with this disease, he added.

EXPAND was a phase 3 study of siponimod. Results showed the now-approved oral selective sphingosine 1–phosphate receptor modulator significantly reduced the risk for disability progression in patients with SPMS.

Using the EXPAND clinical trial database, the current researchers assessed 1,628 participants for an association between cognitive processing speed, as measured with the Symbol Digit Modality Test (SDMT), and physical disability progression, as measured with the Expanded Disability Status Scale (EDSS). A score of 7 or more on the EDSS indicates wheelchair dependence.

Dr. Giovannoni noted that cognitive processing speed is considered an indirect measure of thalamic network efficiency and functional brain reserve.

Investigators looked at both the core study, in which all patients continued on treatment or placebo for up to 37 months, and the core plus extension part, in which patients received treatment for up to 5 years.

They separated SDMT scores into quartiles: from worst (n = 435) to two intermediate quartiles (n = 808) to the best quartile (n = 385).
 

Wheelchair dependence

In addition, the researchers examined the predictive value by baseline SDMT, adjusting for treatment, age, gender, baseline EDSS score, baseline SCMT quartile, and treatment-by-baseline SCMT quartile interaction. On-study SDMT change (month 0-24) was also assessed after adjusting for treatment, age, gender, baseline EDS, baseline SCMT, and on-study change in SCMT quartile.

In the core study, those in the worst SDMT quartile at baseline were numerically more likely to reach deterioration to EDSS 7 or greater (wheelchair dependent), compared with patients in the best SDMT quartile (hazard ratio, 1.31; 95% confidence interval, .72-2.38; P = .371).

The short-term predictive value of baseline SDMT for reaching sustained EDSS of at least 7 was more obvious in the placebo arm than in the treatment arm.

Dr. Giovannoni said this is likely due to the treatment effect of siponimod preventing relatively more events in the worse quartile, and so reducing the risk for wheelchair dependency.

In the core plus extension part, there was an almost twofold increased risk for wheelchair dependence in the worse versus best SDMT groups (HR, 1.81; 95% CI, 1.17-2.78; P = .007).

Both baseline SDMT (HR, 1.81; P = .007) and on-study change in SDMT (HR, 1.73; P = .046) predicted wheelchair dependence in the long-term.
 

‘More important than a walking stick’

Measuring cognitive change over time “may be a more important predictor than a walking stick in terms of quality of life and outcomes, and it affects clinical decisionmaking,” said Dr. Giovannoni.

The findings are not novel, as post hoc analyses of other studies showed similar results. However, this new analysis adds more evidence to the importance of cognition in MS, Dr. Giovannoni noted.

“I have patients with EDSS of 0 or 1 who are profoundly disabled because of cognition. You shouldn’t just assume someone is not disabled because they don’t have physical disability,” he said.

However, Dr. Giovannoni noted that the study found an association and does not necessarily indicate a cause.
 

‘Valuable’ insights

Antonia Lefter, MD, of NeuroHope, Monza Oncologic Hospital, Bucharest, Romania, cochaired the session highlighting the research. Commenting on the study, she called this analysis from the “renowned” EXPAND study “valuable.”

In addition, it “underscores” the importance of assessing cognitive processing speed, as it may predict long-term disability progression in patients with SPMS, Dr. Lefter said.

The study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Giovannoni, a steering committee member of the EXPAND trial, reported receiving consulting fees from AbbVie, Actelion, Atara Bio, Biogen, Celgene, Sanofi-Genzyme, Genentech, GlaxoSmithKline, Merck-Serono, Novartis, Roche, and Reva. He has also received compensation for research from Biogen, Roche, Merck-Serono, Novartis, Sanofi-Genzyme, and Takeda. Dr. Lefter has reported no relevant financial relationships.

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

Among transgender youth who receive puberty-delaying or gender-affirming hormone therapy, bone mineral density (BMD) is lower relative to age-based norms, and this is true regardless of gender assignment at birth.

The problem worsens as the time during which these patients receive sex steroid hormones increases. So far, the “bone mineral density effects of these therapies are understudied,” warned Natalie Nokoff, MD, who presented a cross-sectional study at the annual meeting of the Endocrine Society.

The study of bone density is part of a larger body of research being conducted by Dr. Nokoff and her co-investigators on the long-term health effects of gender-affirming therapy in children and adolescents. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists, which effectively block puberty, were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.

“We need more information on the optimal length of treatment with puberty-delaying medications before either discontinuation or introduction of gender-affirming hormones,” said Dr. Nokoff, an assistant professor of pediatrics and endocrinology at the University of Colorado School of Medicine, Aurora.

In this study, 56 transgender youth underwent total body dual-energy x-ray absorptiometry (DEXA). The patients ranged in age from 10 years to almost 20 years. Just over half (53%) were assigned female sex at birth.

The mean Z scores, signifying deviation from age-matched norms, were lower regardless of current use or past use of GnRH agonists in both transgender males or transgender females, relative to age-matched norms.

Asked to comment, Michele A. O’Connell, MBBCh, department of endocrinology and diabetes, Royal Children’s Hospital, Victoria, Australia, said the risk of bone loss is real.

“Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists,” said Dr. O’Connell. He referred to multiple guidelines, including those issued by the World Professional Association of Transgender Health in 2012 and those from the Endocrine Society that were issued in 2017.
 

Inverse correlation between duration of GnRH agonist therapy and Z scores

In Dr. Nokoff’s study, for transgender males, the BMD Z score was reduced 0.2 relative to male norms and by 0.4 relative to female norms. For transgender females, the scores were reduced by 0.4 relative to male norms and by 0.2 relative to female norms.

Among transgender males who were taking testosterone and who had previously been exposed to GnRH agonists, the Z score was significantly lower than those taking testosterone alone (P = .004). There were no differences in Z score for transgender females taking estradiol alone relative to estradiol with current or past use of GnRH agonists.

There was a significant inverse correlation for duration of GnRH agonist therapy and Z scores for transgender females relative to male norms (P = .005) or female norms (P = .029). However, Z scores were unrelated to length of time receiving testosterone or estradiol therapy or to sex steroid concentrations.

The number of children and adolescents taking puberty-delaying or gender-affirming therapies is increasing. Although reliable data are limited, the exploration of gender identify appears to have become more common with the growing social acceptance of gender dysphoria. That term refers to a sense of unease among individuals who feel that their biological sex does not match their gender identity, according to Dr. Nokoff.

“It is now estimated that 2% of youths identify as transgender,” she said.

Findings from studies investigating the relationship between gender-affirming therapy and bone loss among adults have not been consistent. In a single-center study that followed 543 transgender men and 711 transgender women who had undergone DEXA scanning at baseline prior to starting hormone therapy, there did not appear to be any substantial negative effects on lumbar bone density over time (J Bone Min Res. 2018 Dec;34:447-54).

For adolescents, there is growing evidence of the risk of bone loss in relation to gender-affirming therapy, but there is limited agreement on clinical risks and how they can be avoided. Relevant variables include genetics and diet, as well as the types, doses, and length of time receiving gender-affirming therapy.
 

Monitor bone in transgender youth; Use vitamin D and weight-bearing exercise

Dr. O’Connell is the first author of a recent summary of the pharmacologic management of trans and gender-diverse adolescents. That summary covered multiple topics in addition to risk of bone loss, including the impact on growth, cognition, and mental health (J Clin Endocrinol Metab. 2022 Jan;107:241-257).

Overall, she believes that bone health should be monitored for children receiving puberty-delaying or gender-affirming therapies but agrees with Dr. Nokoff that the clinical impact remains poorly defined.

“Long-term follow-up studies will be required to assess the impact, if any, on functional outcomes such as fracture risk,” she reported. Still, she encouraged use of standard ways of improving bone health, including adequate vitamin D intake and weight-bearing exercise.

Dr. Nokoff and Dr. O’Connell have disclosed no relevant financial relationships.

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

Among transgender youth who receive puberty-delaying or gender-affirming hormone therapy, bone mineral density (BMD) is lower relative to age-based norms, and this is true regardless of gender assignment at birth.

The problem worsens as the time during which these patients receive sex steroid hormones increases. So far, the “bone mineral density effects of these therapies are understudied,” warned Natalie Nokoff, MD, who presented a cross-sectional study at the annual meeting of the Endocrine Society.

The study of bone density is part of a larger body of research being conducted by Dr. Nokoff and her co-investigators on the long-term health effects of gender-affirming therapy in children and adolescents. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists, which effectively block puberty, were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.

“We need more information on the optimal length of treatment with puberty-delaying medications before either discontinuation or introduction of gender-affirming hormones,” said Dr. Nokoff, an assistant professor of pediatrics and endocrinology at the University of Colorado School of Medicine, Aurora.

In this study, 56 transgender youth underwent total body dual-energy x-ray absorptiometry (DEXA). The patients ranged in age from 10 years to almost 20 years. Just over half (53%) were assigned female sex at birth.

The mean Z scores, signifying deviation from age-matched norms, were lower regardless of current use or past use of GnRH agonists in both transgender males or transgender females, relative to age-matched norms.

Asked to comment, Michele A. O’Connell, MBBCh, department of endocrinology and diabetes, Royal Children’s Hospital, Victoria, Australia, said the risk of bone loss is real.

“Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists,” said Dr. O’Connell. He referred to multiple guidelines, including those issued by the World Professional Association of Transgender Health in 2012 and those from the Endocrine Society that were issued in 2017.
 

Inverse correlation between duration of GnRH agonist therapy and Z scores

In Dr. Nokoff’s study, for transgender males, the BMD Z score was reduced 0.2 relative to male norms and by 0.4 relative to female norms. For transgender females, the scores were reduced by 0.4 relative to male norms and by 0.2 relative to female norms.

Among transgender males who were taking testosterone and who had previously been exposed to GnRH agonists, the Z score was significantly lower than those taking testosterone alone (P = .004). There were no differences in Z score for transgender females taking estradiol alone relative to estradiol with current or past use of GnRH agonists.

There was a significant inverse correlation for duration of GnRH agonist therapy and Z scores for transgender females relative to male norms (P = .005) or female norms (P = .029). However, Z scores were unrelated to length of time receiving testosterone or estradiol therapy or to sex steroid concentrations.

The number of children and adolescents taking puberty-delaying or gender-affirming therapies is increasing. Although reliable data are limited, the exploration of gender identify appears to have become more common with the growing social acceptance of gender dysphoria. That term refers to a sense of unease among individuals who feel that their biological sex does not match their gender identity, according to Dr. Nokoff.

“It is now estimated that 2% of youths identify as transgender,” she said.

Findings from studies investigating the relationship between gender-affirming therapy and bone loss among adults have not been consistent. In a single-center study that followed 543 transgender men and 711 transgender women who had undergone DEXA scanning at baseline prior to starting hormone therapy, there did not appear to be any substantial negative effects on lumbar bone density over time (J Bone Min Res. 2018 Dec;34:447-54).

For adolescents, there is growing evidence of the risk of bone loss in relation to gender-affirming therapy, but there is limited agreement on clinical risks and how they can be avoided. Relevant variables include genetics and diet, as well as the types, doses, and length of time receiving gender-affirming therapy.
 

Monitor bone in transgender youth; Use vitamin D and weight-bearing exercise

Dr. O’Connell is the first author of a recent summary of the pharmacologic management of trans and gender-diverse adolescents. That summary covered multiple topics in addition to risk of bone loss, including the impact on growth, cognition, and mental health (J Clin Endocrinol Metab. 2022 Jan;107:241-257).

Overall, she believes that bone health should be monitored for children receiving puberty-delaying or gender-affirming therapies but agrees with Dr. Nokoff that the clinical impact remains poorly defined.

“Long-term follow-up studies will be required to assess the impact, if any, on functional outcomes such as fracture risk,” she reported. Still, she encouraged use of standard ways of improving bone health, including adequate vitamin D intake and weight-bearing exercise.

Dr. Nokoff and Dr. O’Connell have disclosed no relevant financial relationships.

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

Among transgender youth who receive puberty-delaying or gender-affirming hormone therapy, bone mineral density (BMD) is lower relative to age-based norms, and this is true regardless of gender assignment at birth.

The problem worsens as the time during which these patients receive sex steroid hormones increases. So far, the “bone mineral density effects of these therapies are understudied,” warned Natalie Nokoff, MD, who presented a cross-sectional study at the annual meeting of the Endocrine Society.

The study of bone density is part of a larger body of research being conducted by Dr. Nokoff and her co-investigators on the long-term health effects of gender-affirming therapy in children and adolescents. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists, which effectively block puberty, were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.

“We need more information on the optimal length of treatment with puberty-delaying medications before either discontinuation or introduction of gender-affirming hormones,” said Dr. Nokoff, an assistant professor of pediatrics and endocrinology at the University of Colorado School of Medicine, Aurora.

In this study, 56 transgender youth underwent total body dual-energy x-ray absorptiometry (DEXA). The patients ranged in age from 10 years to almost 20 years. Just over half (53%) were assigned female sex at birth.

The mean Z scores, signifying deviation from age-matched norms, were lower regardless of current use or past use of GnRH agonists in both transgender males or transgender females, relative to age-matched norms.

Asked to comment, Michele A. O’Connell, MBBCh, department of endocrinology and diabetes, Royal Children’s Hospital, Victoria, Australia, said the risk of bone loss is real.

“Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists,” said Dr. O’Connell. He referred to multiple guidelines, including those issued by the World Professional Association of Transgender Health in 2012 and those from the Endocrine Society that were issued in 2017.
 

Inverse correlation between duration of GnRH agonist therapy and Z scores

In Dr. Nokoff’s study, for transgender males, the BMD Z score was reduced 0.2 relative to male norms and by 0.4 relative to female norms. For transgender females, the scores were reduced by 0.4 relative to male norms and by 0.2 relative to female norms.

Among transgender males who were taking testosterone and who had previously been exposed to GnRH agonists, the Z score was significantly lower than those taking testosterone alone (P = .004). There were no differences in Z score for transgender females taking estradiol alone relative to estradiol with current or past use of GnRH agonists.

There was a significant inverse correlation for duration of GnRH agonist therapy and Z scores for transgender females relative to male norms (P = .005) or female norms (P = .029). However, Z scores were unrelated to length of time receiving testosterone or estradiol therapy or to sex steroid concentrations.

The number of children and adolescents taking puberty-delaying or gender-affirming therapies is increasing. Although reliable data are limited, the exploration of gender identify appears to have become more common with the growing social acceptance of gender dysphoria. That term refers to a sense of unease among individuals who feel that their biological sex does not match their gender identity, according to Dr. Nokoff.

“It is now estimated that 2% of youths identify as transgender,” she said.

Findings from studies investigating the relationship between gender-affirming therapy and bone loss among adults have not been consistent. In a single-center study that followed 543 transgender men and 711 transgender women who had undergone DEXA scanning at baseline prior to starting hormone therapy, there did not appear to be any substantial negative effects on lumbar bone density over time (J Bone Min Res. 2018 Dec;34:447-54).

For adolescents, there is growing evidence of the risk of bone loss in relation to gender-affirming therapy, but there is limited agreement on clinical risks and how they can be avoided. Relevant variables include genetics and diet, as well as the types, doses, and length of time receiving gender-affirming therapy.
 

Monitor bone in transgender youth; Use vitamin D and weight-bearing exercise

Dr. O’Connell is the first author of a recent summary of the pharmacologic management of trans and gender-diverse adolescents. That summary covered multiple topics in addition to risk of bone loss, including the impact on growth, cognition, and mental health (J Clin Endocrinol Metab. 2022 Jan;107:241-257).

Overall, she believes that bone health should be monitored for children receiving puberty-delaying or gender-affirming therapies but agrees with Dr. Nokoff that the clinical impact remains poorly defined.

“Long-term follow-up studies will be required to assess the impact, if any, on functional outcomes such as fracture risk,” she reported. Still, she encouraged use of standard ways of improving bone health, including adequate vitamin D intake and weight-bearing exercise.

Dr. Nokoff and Dr. O’Connell have disclosed no relevant financial relationships.

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

GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.

Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.

Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.

The most common delayed events were pityriasis rosea and lichen planus, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.

Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.

She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.

Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.

She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.

Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.

She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.

They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.

The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.

Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.

This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.

The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.

There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.

The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.

Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.

Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.

Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.

Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.

Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”

He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”

Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)

She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”

Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”

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

GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.

Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.

Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.

The most common delayed events were pityriasis rosea and lichen planus, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.

Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.

She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.

Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.

She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.

Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.

She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.

They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.

The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.

Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.

This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.

The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.

There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.

The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.

Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.

Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.

Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.

Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.

Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”

He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”

Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)

She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”

Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”

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

GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.

Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.

Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.

The most common delayed events were pityriasis rosea and lichen planus, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.

Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.

She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.

Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.

She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.

Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.

She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.

They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.

The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.

Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.

This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.

The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.

There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.

The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.

Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.

Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.

Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.

Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.

Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”

He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”

Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)

She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”

Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”

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

GLASGOW – Dermatologists do not feel confident in independently prescribing antipsychotic medications for patients with delusional infestation, shows a U.K. survey that also indicated there is a clear demand for training in prescribing these drugs.

Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.

The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.

This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.

Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.

This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”

Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”

The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.

Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.

Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.

Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).

The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.

Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.

The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.

In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.

An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.

However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.

Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.

She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.

In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”

Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.

Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”

She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”

Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”

No funding or relevant financial relationships were declared.

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

GLASGOW – Dermatologists do not feel confident in independently prescribing antipsychotic medications for patients with delusional infestation, shows a U.K. survey that also indicated there is a clear demand for training in prescribing these drugs.

Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.

The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.

This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.

Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.

This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”

Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”

The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.

Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.

Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.

Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).

The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.

Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.

The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.

In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.

An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.

However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.

Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.

She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.

In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”

Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.

Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”

She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”

Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”

No funding or relevant financial relationships were declared.

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

GLASGOW – Dermatologists do not feel confident in independently prescribing antipsychotic medications for patients with delusional infestation, shows a U.K. survey that also indicated there is a clear demand for training in prescribing these drugs.

Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.

The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.

This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.

Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.

This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”

Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”

The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.

Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.

Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.

Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).

The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.

Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.

The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.

In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.

An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.

However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.

Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.

She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.

In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”

Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.

Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”

She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”

Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”

No funding or relevant financial relationships were declared.

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