User login
Study compares pulse vs. continuous therapy for dermatophyte toenail onychomycosis
There appear to be results from a systematic review and network meta-analysis showed.
“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”
In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.
For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.
“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”
They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”
The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.
SOURCE: Gupta A et al. AAD 20, Abstract 16014.
There appear to be results from a systematic review and network meta-analysis showed.
“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”
In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.
For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.
“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”
They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”
The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.
SOURCE: Gupta A et al. AAD 20, Abstract 16014.
There appear to be results from a systematic review and network meta-analysis showed.
“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”
In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.
For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.
“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”
They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”
The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.
SOURCE: Gupta A et al. AAD 20, Abstract 16014.
FROM AAD 20
High-fat, high-sugar diet may promote adult acne
A diet higher in fat, sugar, and milk was associated with having acne in a cross-sectional study of approximately 24,000 adults in France.
Acne in adults has been associated with social, emotional, and psychological consequences similar to those found with chronic diseases such as asthma, arthritis, epilepsy, and diabetes, wrote Laetitia Penso, MSc, of the University of Paris in Bobigny, France, and colleagues.
Although acne patients may believe that eating certain foods exacerbates acne, data on the effects of nutrition on acne, including associations between acne and a high-glycemic diet, are limited and have produced conflicting results, they noted.
In their study, published in JAMA Dermatology, the researchers identified 24,452 adults who participated in the NutriNet-Santé study, an ongoing, web-based study in France. Approximately 75% of the participants were women, the average age was 57 years, and 46% reported past or current acne.
Participants responded to an 11-item questionnaire between November 2008 and July 2019. Questions were related to the occurrence and diagnosis of acne, as well as medical history. Based on their acne status, participants were identified as falling into the categories of never acne, past acne, or current acne, and their dietary intake was assessed at baseline and every 6 months using three nonconsecutive 24-hour dietary records for 2 weekdays and 1 weekend day.
In an analysis, after adjustment for confounders, current acne was significantly associated with consumption of fatty and sugary foods (per portion, adjusted odds ratio, 1.54; P = .01), as well as with consumption of sugary drinks (per glass, aOR, 1.18; P = .04) and milk (per glass, aOR, 1.12; P = .04). In addition, carbohydrate intake and saturated fatty acid intake were significantly associated with current acne (aOR, 1.43; P = .02; and aOR, 3.90; P = .048, respectively).
Three dietary patterns accounted for 42% of the total variability, the researchers said. A healthy pattern of higher fruit, vegetable, and fish intake accounted for 18%, a fatty and sugary pattern of higher fat and sugar intake (including chocolate) accounted for 13%, and an animal product and cereal pattern of higher intake of meat, milk, and refined cereals accounted for 11%, they explained.
“The results of our study appear to support the hypothesis that the Western diet (rich in animal products and fatty and sugary foods) is associated with the presence of acne in adulthood,” the researchers concluded. Possible explanations for the findings include the effects of a high glycemic-load diet on circulating IGF-1 and insulin, which ultimately increases both oxidative stress and inflammation that promotes the development of acne, they noted.
The study findings were limited by several factors including the use of relatively homogenous younger and female patient population and the reliance on self-reported acne, as well as the observational design, which did not allow for identification of direct, causal associations between diet and acne, the researchers noted. Larger studies are needed to examine the relationship between diet and adult acne to inform prevention and treatment, they wrote.
“Much of the previous literature on the role of diet in acne has focused on the association of milk consumption and high glycemic-load diet with acne,” John S. Barbieri, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.
Dr. Barbieri acknowledged the inability to make causal associations given the study design and noted that dietary interventions should be implemented with caution because of the potential for other effects such as reduced calcium or vitamin D.
“Nevertheless, given the potential overall health benefits of a healthy or low glycemic-load diet, and 2 small trials supporting its effectiveness in acne, a low glycemic-load diet is a reasonable recommendation for patients looking for dietary modifications that may improve their acne,” he said.
Dr. Barbieri said that he was encouraged to see that the study findings reflected previous research identifying an association between acne and high-glycemic load foods, as well as milk consumption, but he emphasized that more research is needed before general recommendations about diet and acne can be made.
“Trials are needed to evaluate whether dietary interventions can improve or prevent acne and how the effect size of such interventions compares with other standard treatment modalities,” he emphasized.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Barbieri disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and from a Pfizer Fellowship grant to the Trustees of the University of Pennsylvania.
SOURCE: Penso L et al. JAMA Dermatol. 2020 June 10. doi: 10.1001/jamadermatol.2020.1602.
A diet higher in fat, sugar, and milk was associated with having acne in a cross-sectional study of approximately 24,000 adults in France.
Acne in adults has been associated with social, emotional, and psychological consequences similar to those found with chronic diseases such as asthma, arthritis, epilepsy, and diabetes, wrote Laetitia Penso, MSc, of the University of Paris in Bobigny, France, and colleagues.
Although acne patients may believe that eating certain foods exacerbates acne, data on the effects of nutrition on acne, including associations between acne and a high-glycemic diet, are limited and have produced conflicting results, they noted.
In their study, published in JAMA Dermatology, the researchers identified 24,452 adults who participated in the NutriNet-Santé study, an ongoing, web-based study in France. Approximately 75% of the participants were women, the average age was 57 years, and 46% reported past or current acne.
Participants responded to an 11-item questionnaire between November 2008 and July 2019. Questions were related to the occurrence and diagnosis of acne, as well as medical history. Based on their acne status, participants were identified as falling into the categories of never acne, past acne, or current acne, and their dietary intake was assessed at baseline and every 6 months using three nonconsecutive 24-hour dietary records for 2 weekdays and 1 weekend day.
In an analysis, after adjustment for confounders, current acne was significantly associated with consumption of fatty and sugary foods (per portion, adjusted odds ratio, 1.54; P = .01), as well as with consumption of sugary drinks (per glass, aOR, 1.18; P = .04) and milk (per glass, aOR, 1.12; P = .04). In addition, carbohydrate intake and saturated fatty acid intake were significantly associated with current acne (aOR, 1.43; P = .02; and aOR, 3.90; P = .048, respectively).
Three dietary patterns accounted for 42% of the total variability, the researchers said. A healthy pattern of higher fruit, vegetable, and fish intake accounted for 18%, a fatty and sugary pattern of higher fat and sugar intake (including chocolate) accounted for 13%, and an animal product and cereal pattern of higher intake of meat, milk, and refined cereals accounted for 11%, they explained.
“The results of our study appear to support the hypothesis that the Western diet (rich in animal products and fatty and sugary foods) is associated with the presence of acne in adulthood,” the researchers concluded. Possible explanations for the findings include the effects of a high glycemic-load diet on circulating IGF-1 and insulin, which ultimately increases both oxidative stress and inflammation that promotes the development of acne, they noted.
The study findings were limited by several factors including the use of relatively homogenous younger and female patient population and the reliance on self-reported acne, as well as the observational design, which did not allow for identification of direct, causal associations between diet and acne, the researchers noted. Larger studies are needed to examine the relationship between diet and adult acne to inform prevention and treatment, they wrote.
“Much of the previous literature on the role of diet in acne has focused on the association of milk consumption and high glycemic-load diet with acne,” John S. Barbieri, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.
Dr. Barbieri acknowledged the inability to make causal associations given the study design and noted that dietary interventions should be implemented with caution because of the potential for other effects such as reduced calcium or vitamin D.
“Nevertheless, given the potential overall health benefits of a healthy or low glycemic-load diet, and 2 small trials supporting its effectiveness in acne, a low glycemic-load diet is a reasonable recommendation for patients looking for dietary modifications that may improve their acne,” he said.
Dr. Barbieri said that he was encouraged to see that the study findings reflected previous research identifying an association between acne and high-glycemic load foods, as well as milk consumption, but he emphasized that more research is needed before general recommendations about diet and acne can be made.
“Trials are needed to evaluate whether dietary interventions can improve or prevent acne and how the effect size of such interventions compares with other standard treatment modalities,” he emphasized.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Barbieri disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and from a Pfizer Fellowship grant to the Trustees of the University of Pennsylvania.
SOURCE: Penso L et al. JAMA Dermatol. 2020 June 10. doi: 10.1001/jamadermatol.2020.1602.
A diet higher in fat, sugar, and milk was associated with having acne in a cross-sectional study of approximately 24,000 adults in France.
Acne in adults has been associated with social, emotional, and psychological consequences similar to those found with chronic diseases such as asthma, arthritis, epilepsy, and diabetes, wrote Laetitia Penso, MSc, of the University of Paris in Bobigny, France, and colleagues.
Although acne patients may believe that eating certain foods exacerbates acne, data on the effects of nutrition on acne, including associations between acne and a high-glycemic diet, are limited and have produced conflicting results, they noted.
In their study, published in JAMA Dermatology, the researchers identified 24,452 adults who participated in the NutriNet-Santé study, an ongoing, web-based study in France. Approximately 75% of the participants were women, the average age was 57 years, and 46% reported past or current acne.
Participants responded to an 11-item questionnaire between November 2008 and July 2019. Questions were related to the occurrence and diagnosis of acne, as well as medical history. Based on their acne status, participants were identified as falling into the categories of never acne, past acne, or current acne, and their dietary intake was assessed at baseline and every 6 months using three nonconsecutive 24-hour dietary records for 2 weekdays and 1 weekend day.
In an analysis, after adjustment for confounders, current acne was significantly associated with consumption of fatty and sugary foods (per portion, adjusted odds ratio, 1.54; P = .01), as well as with consumption of sugary drinks (per glass, aOR, 1.18; P = .04) and milk (per glass, aOR, 1.12; P = .04). In addition, carbohydrate intake and saturated fatty acid intake were significantly associated with current acne (aOR, 1.43; P = .02; and aOR, 3.90; P = .048, respectively).
Three dietary patterns accounted for 42% of the total variability, the researchers said. A healthy pattern of higher fruit, vegetable, and fish intake accounted for 18%, a fatty and sugary pattern of higher fat and sugar intake (including chocolate) accounted for 13%, and an animal product and cereal pattern of higher intake of meat, milk, and refined cereals accounted for 11%, they explained.
“The results of our study appear to support the hypothesis that the Western diet (rich in animal products and fatty and sugary foods) is associated with the presence of acne in adulthood,” the researchers concluded. Possible explanations for the findings include the effects of a high glycemic-load diet on circulating IGF-1 and insulin, which ultimately increases both oxidative stress and inflammation that promotes the development of acne, they noted.
The study findings were limited by several factors including the use of relatively homogenous younger and female patient population and the reliance on self-reported acne, as well as the observational design, which did not allow for identification of direct, causal associations between diet and acne, the researchers noted. Larger studies are needed to examine the relationship between diet and adult acne to inform prevention and treatment, they wrote.
“Much of the previous literature on the role of diet in acne has focused on the association of milk consumption and high glycemic-load diet with acne,” John S. Barbieri, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.
Dr. Barbieri acknowledged the inability to make causal associations given the study design and noted that dietary interventions should be implemented with caution because of the potential for other effects such as reduced calcium or vitamin D.
“Nevertheless, given the potential overall health benefits of a healthy or low glycemic-load diet, and 2 small trials supporting its effectiveness in acne, a low glycemic-load diet is a reasonable recommendation for patients looking for dietary modifications that may improve their acne,” he said.
Dr. Barbieri said that he was encouraged to see that the study findings reflected previous research identifying an association between acne and high-glycemic load foods, as well as milk consumption, but he emphasized that more research is needed before general recommendations about diet and acne can be made.
“Trials are needed to evaluate whether dietary interventions can improve or prevent acne and how the effect size of such interventions compares with other standard treatment modalities,” he emphasized.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Barbieri disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and from a Pfizer Fellowship grant to the Trustees of the University of Pennsylvania.
SOURCE: Penso L et al. JAMA Dermatol. 2020 June 10. doi: 10.1001/jamadermatol.2020.1602.
FROM JAMA DERMATOLOGY
Tralokinumab found effective in phase 3 atopic dermatitis studies
presented at the virtual annual meeting of the American Academy of Dermatology.
Tralokinumab is a fully human monoclonal antibody which binds specifically to interleukin-13 and thereby prevents downstream IL-13 signaling. In contrast, dupilumab (Dupixent), at present the only approved biologic agent for AD, blocks both the IL-13 and IL-4 pathways.
Two of the pivotal phase 3 trials presented at AAD 2020 – ECZTRA 1 and ECZTRA 2 – were identically designed, randomized, double-blind, placebo-controlled, 52-week, multinational monotherapy studies including a collective 1,596 adults with moderate to severe AD. In contrast, ECZTRA 3 was a 380-patient, double-blind, randomized, 32-week study of tralokinumab in combination with a topical corticosteroid versus placebo injections plus a topical corticosteroid.
“I would say the take-home point of these trials is they are proof of principle that blocking just IL-13 can be an effective approach. The studies help us understand that IL-13 is an important driver cytokine for the disease,” Eric Simpson, MD, lead clinical investigator for ECZTRA 2, said in an interview.
In all three phase 3 trials, the primary endpoint was achievement of a clinical response as defined by an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) plus at least a 75% improvement in the Eczema Area and Severity Index score (EASI-75) at week 16. In ECZTRA 1 and 2, this was accomplished in 16% and 22% of patients on 300 mg of tralokinumab administered subcutaneously every 2 weeks, compared with 7% and 11% of placebo-treated controls.
Patients with a clinical response at week 16 were then rerandomized to tralokinumab either every other week or every 4 weeks or to placebo for an additional 36 weeks. At 52 weeks, 51% and 59% of patients in ECZTRA 1 and 2, respectively, who had a clinical response at week 16 maintained an IGA 0/1 response while on tralokinumab every 2 weeks, as did 39% and 45% of those switched to treatment every 4 weeks. Similarly, 60% and 56% of clinical responders at week 16 maintained an EASI-75 response at week 52 with tralokinumab every 2 weeks, as did 49% and 51% of those rerandomized to treatment every 4 weeks.
The safety profile of tralokinumab in the two monotherapy trials was comparable with placebo.
In the ECZTRA studies, tralokinumab achieved significant improvement at week 16 in secondary endpoints including itch, health-related quality of life, and severity and extent of skin lesions.
How does tralokinumab, with its narrower focus targeting a single cytokine, stack up against dupilumab, the dual IL-13/IL-4 inhibitor that’s transformed the treatment of patients with moderate or severe AD?
Dr. Simpson, who was also principal investigator in a pivotal phase 3 trial for dupilumab, emphasized that no firm conclusions can be drawn because there have been no head-to-head comparative trials and the tralokinumab and dupilumab trials had different patient populations, geographic locations, and washout periods. With those caveats, however, he commented that, “just on the surface, numerically, for the monotherapy studies, dupilumab hit some higher targets than tralokinumab in terms of the percentage of patients clear or almost clear.”
In terms of safety, it appears that the risk of conjunctivitis may be lower with tralokinumab than dupilumab, with rates of 7% and 3% through 52 weeks in ECZTRA 1 and 2, respectively, versus 2% with placebo, although again this is “a caveated conclusion,” said Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland.
Tralokinumab combination therapy in ECZTRA 3
At 16 weeks, 39% of patients treated with tralokinumab plus topical corticosteroids had an IGA of 0/1 and 56% had an EASI-75 response, compared with 26% and 36% of patients on topical corticosteroids plus biweekly placebo injections. More than 90% of patients with a good clinical response at week 16 maintained that response at week 32 while on tralokinumab biweekly plus topical steroids. Among good responders at week 16 who were rerandomized to 300 mg of tralokinumab every 4 weeks plus topical steroids, 78% still had an IGA of 0/1 at week 32, and 91% had an EASI-75, reported Jonathan I. Silverberg, MD, PhD, director of clinical research and contact dermatitis at George Washington University, Washington.
A randomized, placebo-controlled combination therapy study such as this provides information that’s especially useful in clinical practice, Dr. Simpson observed.
“When I’m talking to patients about any biologics or oral therapies, I usually quote the figures from the combination therapy studies because the vast majority of our patients are using topical therapy in addition to systemics,” he said in the interview.
Asked how he envisions tralokinumab’s role in clinical practice, should the drug receive regulatory approval, Dr. Simpson said that he welcomes the prospect of having an additional treatment option to discuss with patients. Tralokinumab could be considered either as first-line therapy in patients who are failing on topical therapy or for patients who don’t respond adequately to or experience limiting side effects on dupilumab.
“There isn’t any established, published treatment algorithm in atopic dermatitis, probably for good reason, since we don’t have data to tell us you should start here and then move there. Those are long, difficult studies to perform,” Dr. Simpson said.
LEO Pharma has announced that it has applied for marketing approval for tralokinumab to the European Medicines Agency and plans to do so with the Food and Drug Administration by year’s end.
Dr. Simpson reported receiving research grants from and serving as a consultant to LEO Pharma, sponsor of the ECZTRA trials. He has similar financial relationships with close to a dozen other pharmaceutical companies.
presented at the virtual annual meeting of the American Academy of Dermatology.
Tralokinumab is a fully human monoclonal antibody which binds specifically to interleukin-13 and thereby prevents downstream IL-13 signaling. In contrast, dupilumab (Dupixent), at present the only approved biologic agent for AD, blocks both the IL-13 and IL-4 pathways.
Two of the pivotal phase 3 trials presented at AAD 2020 – ECZTRA 1 and ECZTRA 2 – were identically designed, randomized, double-blind, placebo-controlled, 52-week, multinational monotherapy studies including a collective 1,596 adults with moderate to severe AD. In contrast, ECZTRA 3 was a 380-patient, double-blind, randomized, 32-week study of tralokinumab in combination with a topical corticosteroid versus placebo injections plus a topical corticosteroid.
“I would say the take-home point of these trials is they are proof of principle that blocking just IL-13 can be an effective approach. The studies help us understand that IL-13 is an important driver cytokine for the disease,” Eric Simpson, MD, lead clinical investigator for ECZTRA 2, said in an interview.
In all three phase 3 trials, the primary endpoint was achievement of a clinical response as defined by an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) plus at least a 75% improvement in the Eczema Area and Severity Index score (EASI-75) at week 16. In ECZTRA 1 and 2, this was accomplished in 16% and 22% of patients on 300 mg of tralokinumab administered subcutaneously every 2 weeks, compared with 7% and 11% of placebo-treated controls.
Patients with a clinical response at week 16 were then rerandomized to tralokinumab either every other week or every 4 weeks or to placebo for an additional 36 weeks. At 52 weeks, 51% and 59% of patients in ECZTRA 1 and 2, respectively, who had a clinical response at week 16 maintained an IGA 0/1 response while on tralokinumab every 2 weeks, as did 39% and 45% of those switched to treatment every 4 weeks. Similarly, 60% and 56% of clinical responders at week 16 maintained an EASI-75 response at week 52 with tralokinumab every 2 weeks, as did 49% and 51% of those rerandomized to treatment every 4 weeks.
The safety profile of tralokinumab in the two monotherapy trials was comparable with placebo.
In the ECZTRA studies, tralokinumab achieved significant improvement at week 16 in secondary endpoints including itch, health-related quality of life, and severity and extent of skin lesions.
How does tralokinumab, with its narrower focus targeting a single cytokine, stack up against dupilumab, the dual IL-13/IL-4 inhibitor that’s transformed the treatment of patients with moderate or severe AD?
Dr. Simpson, who was also principal investigator in a pivotal phase 3 trial for dupilumab, emphasized that no firm conclusions can be drawn because there have been no head-to-head comparative trials and the tralokinumab and dupilumab trials had different patient populations, geographic locations, and washout periods. With those caveats, however, he commented that, “just on the surface, numerically, for the monotherapy studies, dupilumab hit some higher targets than tralokinumab in terms of the percentage of patients clear or almost clear.”
In terms of safety, it appears that the risk of conjunctivitis may be lower with tralokinumab than dupilumab, with rates of 7% and 3% through 52 weeks in ECZTRA 1 and 2, respectively, versus 2% with placebo, although again this is “a caveated conclusion,” said Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland.
Tralokinumab combination therapy in ECZTRA 3
At 16 weeks, 39% of patients treated with tralokinumab plus topical corticosteroids had an IGA of 0/1 and 56% had an EASI-75 response, compared with 26% and 36% of patients on topical corticosteroids plus biweekly placebo injections. More than 90% of patients with a good clinical response at week 16 maintained that response at week 32 while on tralokinumab biweekly plus topical steroids. Among good responders at week 16 who were rerandomized to 300 mg of tralokinumab every 4 weeks plus topical steroids, 78% still had an IGA of 0/1 at week 32, and 91% had an EASI-75, reported Jonathan I. Silverberg, MD, PhD, director of clinical research and contact dermatitis at George Washington University, Washington.
A randomized, placebo-controlled combination therapy study such as this provides information that’s especially useful in clinical practice, Dr. Simpson observed.
“When I’m talking to patients about any biologics or oral therapies, I usually quote the figures from the combination therapy studies because the vast majority of our patients are using topical therapy in addition to systemics,” he said in the interview.
Asked how he envisions tralokinumab’s role in clinical practice, should the drug receive regulatory approval, Dr. Simpson said that he welcomes the prospect of having an additional treatment option to discuss with patients. Tralokinumab could be considered either as first-line therapy in patients who are failing on topical therapy or for patients who don’t respond adequately to or experience limiting side effects on dupilumab.
“There isn’t any established, published treatment algorithm in atopic dermatitis, probably for good reason, since we don’t have data to tell us you should start here and then move there. Those are long, difficult studies to perform,” Dr. Simpson said.
LEO Pharma has announced that it has applied for marketing approval for tralokinumab to the European Medicines Agency and plans to do so with the Food and Drug Administration by year’s end.
Dr. Simpson reported receiving research grants from and serving as a consultant to LEO Pharma, sponsor of the ECZTRA trials. He has similar financial relationships with close to a dozen other pharmaceutical companies.
presented at the virtual annual meeting of the American Academy of Dermatology.
Tralokinumab is a fully human monoclonal antibody which binds specifically to interleukin-13 and thereby prevents downstream IL-13 signaling. In contrast, dupilumab (Dupixent), at present the only approved biologic agent for AD, blocks both the IL-13 and IL-4 pathways.
Two of the pivotal phase 3 trials presented at AAD 2020 – ECZTRA 1 and ECZTRA 2 – were identically designed, randomized, double-blind, placebo-controlled, 52-week, multinational monotherapy studies including a collective 1,596 adults with moderate to severe AD. In contrast, ECZTRA 3 was a 380-patient, double-blind, randomized, 32-week study of tralokinumab in combination with a topical corticosteroid versus placebo injections plus a topical corticosteroid.
“I would say the take-home point of these trials is they are proof of principle that blocking just IL-13 can be an effective approach. The studies help us understand that IL-13 is an important driver cytokine for the disease,” Eric Simpson, MD, lead clinical investigator for ECZTRA 2, said in an interview.
In all three phase 3 trials, the primary endpoint was achievement of a clinical response as defined by an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) plus at least a 75% improvement in the Eczema Area and Severity Index score (EASI-75) at week 16. In ECZTRA 1 and 2, this was accomplished in 16% and 22% of patients on 300 mg of tralokinumab administered subcutaneously every 2 weeks, compared with 7% and 11% of placebo-treated controls.
Patients with a clinical response at week 16 were then rerandomized to tralokinumab either every other week or every 4 weeks or to placebo for an additional 36 weeks. At 52 weeks, 51% and 59% of patients in ECZTRA 1 and 2, respectively, who had a clinical response at week 16 maintained an IGA 0/1 response while on tralokinumab every 2 weeks, as did 39% and 45% of those switched to treatment every 4 weeks. Similarly, 60% and 56% of clinical responders at week 16 maintained an EASI-75 response at week 52 with tralokinumab every 2 weeks, as did 49% and 51% of those rerandomized to treatment every 4 weeks.
The safety profile of tralokinumab in the two monotherapy trials was comparable with placebo.
In the ECZTRA studies, tralokinumab achieved significant improvement at week 16 in secondary endpoints including itch, health-related quality of life, and severity and extent of skin lesions.
How does tralokinumab, with its narrower focus targeting a single cytokine, stack up against dupilumab, the dual IL-13/IL-4 inhibitor that’s transformed the treatment of patients with moderate or severe AD?
Dr. Simpson, who was also principal investigator in a pivotal phase 3 trial for dupilumab, emphasized that no firm conclusions can be drawn because there have been no head-to-head comparative trials and the tralokinumab and dupilumab trials had different patient populations, geographic locations, and washout periods. With those caveats, however, he commented that, “just on the surface, numerically, for the monotherapy studies, dupilumab hit some higher targets than tralokinumab in terms of the percentage of patients clear or almost clear.”
In terms of safety, it appears that the risk of conjunctivitis may be lower with tralokinumab than dupilumab, with rates of 7% and 3% through 52 weeks in ECZTRA 1 and 2, respectively, versus 2% with placebo, although again this is “a caveated conclusion,” said Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland.
Tralokinumab combination therapy in ECZTRA 3
At 16 weeks, 39% of patients treated with tralokinumab plus topical corticosteroids had an IGA of 0/1 and 56% had an EASI-75 response, compared with 26% and 36% of patients on topical corticosteroids plus biweekly placebo injections. More than 90% of patients with a good clinical response at week 16 maintained that response at week 32 while on tralokinumab biweekly plus topical steroids. Among good responders at week 16 who were rerandomized to 300 mg of tralokinumab every 4 weeks plus topical steroids, 78% still had an IGA of 0/1 at week 32, and 91% had an EASI-75, reported Jonathan I. Silverberg, MD, PhD, director of clinical research and contact dermatitis at George Washington University, Washington.
A randomized, placebo-controlled combination therapy study such as this provides information that’s especially useful in clinical practice, Dr. Simpson observed.
“When I’m talking to patients about any biologics or oral therapies, I usually quote the figures from the combination therapy studies because the vast majority of our patients are using topical therapy in addition to systemics,” he said in the interview.
Asked how he envisions tralokinumab’s role in clinical practice, should the drug receive regulatory approval, Dr. Simpson said that he welcomes the prospect of having an additional treatment option to discuss with patients. Tralokinumab could be considered either as first-line therapy in patients who are failing on topical therapy or for patients who don’t respond adequately to or experience limiting side effects on dupilumab.
“There isn’t any established, published treatment algorithm in atopic dermatitis, probably for good reason, since we don’t have data to tell us you should start here and then move there. Those are long, difficult studies to perform,” Dr. Simpson said.
LEO Pharma has announced that it has applied for marketing approval for tralokinumab to the European Medicines Agency and plans to do so with the Food and Drug Administration by year’s end.
Dr. Simpson reported receiving research grants from and serving as a consultant to LEO Pharma, sponsor of the ECZTRA trials. He has similar financial relationships with close to a dozen other pharmaceutical companies.
FROM AAD 2020
Study spotlights the skin microbiome’s evolving nature
, while the skin microbiome of the mothers of the children whose microbiome was analyzed remained relatively constant over the same time period.
The findings come from what is believed to be the longest longitudinal study specific to the skin microbiome of infants and mothers.
“Even at 10 years, the skin microbiome does not look like an adult skin microbiome, based on composition of the ecosystem,” lead author Kimberly A. Capone, PhD, said in an interview during the virtual annual meeting of the American Academy of Dermatology. “The diversity of the microbiome in children’s skin is distinct to that of an adult’s skin. We all have the same bacteria present, but in children it is distributed differently because the bacteria set themselves up based on the nutrients and topography that they find on the skin. Since infant skin is unique to infants, so too is their microbiome when we compare it to adults. It’s been fascinating to observe these children grow and mature, and follow the skin microbiome along this same period.”
During five time points over a period of 10 years, Dr. Capone and her colleagues at the Skillman, N.J.–based Johnson & Johnson Consumer Experience Center, a research and development site, used 16s rRNA gene sequencing to evaluate the skin microbiome on the forearms and foreheads of 30 mothers and their 31 children. The study participants had Fitzpatrick skin types I-IV and the mean age of mothers was 37 years. “We used 16s rRNA gene sequencing for microbiome analysis at the beginning, as that was what was available 10 years ago,” said Dr. Capone, head of the microbiome platform for Johnson & Johnson Consumer Health. “Since then, we continue to use 16s for continuity, but also collected additional swabs for deeper analysis later.”
She and her colleagues often draw samples from the forearm in baby skin clinical studies, “as the arm is a good site to collect relevant data on the body overall,” she explained. “We chose the forearm and forehead specifically here so we can make same body site comparisons to adult sample data which we took from the mothers on the same areas of their body.” Time point 1 was 3 months to 1 year, time point 2 was 2-3 years, time point 3 was 5-6 years, time point 4 was 7-8 years, and time point 5 was 9-10 years.
The researchers found that the skin of infants during the first few weeks of life was similar at age 3 and 4 years. “From that second time point on, we see significant increases in richness and diversity, richness being presence or absence of various bacterial species, and diversity being the relative abundance of those species,” Dr. Capone said. “What you’re basically seeing is that there are new organisms, i.e., richness, coming into the microbiome. We start to detect new ones. Over time, the ecosystem is expanding. It’s evolving because it’s not yet set up.” The evolving skin microbiome on children was dominated by Streptococcus and Staphylococcus. In addition, children had higher levels of Streptococcus, Moraxella, Granulicatella, Gemella and Veillonella, compared with their adult mothers. Adult skin was colonized predominantly by Propionibacterium/Cutibacterium and Staphylococcus.
“The skin microbiome also increased in diversity over time on the forearm, but not face, of the mothers,” Dr. Capone said. “Previous studies have shown how stable the adult skin microbiome is, so it’s intriguing to see the changes that we saw on the mothers in this study.”
The increase in skin microbiome diversity observed in the children is likely due to a variety of factors, she continued, including inherent growth and development, dietary changes, as well as exposure to various environments and other people. “The fact remains that diversity is increasing over time, as the ecosystem evolves,” she said. “Eventually, the skin microbiome will become ‘adultlike’ in puberty, when lipid production increases. This drives increases in Cutibacterium acnes, particularly on the face.”
She acknowledged certain limitations of the study, including its relatively small size and the fact that some of the original subjects did not return for microbiome analysis at later time points. “We need larger cohort studies, additional deeper sequence data, metabolomics and transcriptomics to better understand the function of the skin microbiome over these various ages,” she said.
The study was sponsored by Johnson & Johnson Consumer. Dr. Capone and her two coauthors are employees of the company.
, while the skin microbiome of the mothers of the children whose microbiome was analyzed remained relatively constant over the same time period.
The findings come from what is believed to be the longest longitudinal study specific to the skin microbiome of infants and mothers.
“Even at 10 years, the skin microbiome does not look like an adult skin microbiome, based on composition of the ecosystem,” lead author Kimberly A. Capone, PhD, said in an interview during the virtual annual meeting of the American Academy of Dermatology. “The diversity of the microbiome in children’s skin is distinct to that of an adult’s skin. We all have the same bacteria present, but in children it is distributed differently because the bacteria set themselves up based on the nutrients and topography that they find on the skin. Since infant skin is unique to infants, so too is their microbiome when we compare it to adults. It’s been fascinating to observe these children grow and mature, and follow the skin microbiome along this same period.”
During five time points over a period of 10 years, Dr. Capone and her colleagues at the Skillman, N.J.–based Johnson & Johnson Consumer Experience Center, a research and development site, used 16s rRNA gene sequencing to evaluate the skin microbiome on the forearms and foreheads of 30 mothers and their 31 children. The study participants had Fitzpatrick skin types I-IV and the mean age of mothers was 37 years. “We used 16s rRNA gene sequencing for microbiome analysis at the beginning, as that was what was available 10 years ago,” said Dr. Capone, head of the microbiome platform for Johnson & Johnson Consumer Health. “Since then, we continue to use 16s for continuity, but also collected additional swabs for deeper analysis later.”
She and her colleagues often draw samples from the forearm in baby skin clinical studies, “as the arm is a good site to collect relevant data on the body overall,” she explained. “We chose the forearm and forehead specifically here so we can make same body site comparisons to adult sample data which we took from the mothers on the same areas of their body.” Time point 1 was 3 months to 1 year, time point 2 was 2-3 years, time point 3 was 5-6 years, time point 4 was 7-8 years, and time point 5 was 9-10 years.
The researchers found that the skin of infants during the first few weeks of life was similar at age 3 and 4 years. “From that second time point on, we see significant increases in richness and diversity, richness being presence or absence of various bacterial species, and diversity being the relative abundance of those species,” Dr. Capone said. “What you’re basically seeing is that there are new organisms, i.e., richness, coming into the microbiome. We start to detect new ones. Over time, the ecosystem is expanding. It’s evolving because it’s not yet set up.” The evolving skin microbiome on children was dominated by Streptococcus and Staphylococcus. In addition, children had higher levels of Streptococcus, Moraxella, Granulicatella, Gemella and Veillonella, compared with their adult mothers. Adult skin was colonized predominantly by Propionibacterium/Cutibacterium and Staphylococcus.
“The skin microbiome also increased in diversity over time on the forearm, but not face, of the mothers,” Dr. Capone said. “Previous studies have shown how stable the adult skin microbiome is, so it’s intriguing to see the changes that we saw on the mothers in this study.”
The increase in skin microbiome diversity observed in the children is likely due to a variety of factors, she continued, including inherent growth and development, dietary changes, as well as exposure to various environments and other people. “The fact remains that diversity is increasing over time, as the ecosystem evolves,” she said. “Eventually, the skin microbiome will become ‘adultlike’ in puberty, when lipid production increases. This drives increases in Cutibacterium acnes, particularly on the face.”
She acknowledged certain limitations of the study, including its relatively small size and the fact that some of the original subjects did not return for microbiome analysis at later time points. “We need larger cohort studies, additional deeper sequence data, metabolomics and transcriptomics to better understand the function of the skin microbiome over these various ages,” she said.
The study was sponsored by Johnson & Johnson Consumer. Dr. Capone and her two coauthors are employees of the company.
, while the skin microbiome of the mothers of the children whose microbiome was analyzed remained relatively constant over the same time period.
The findings come from what is believed to be the longest longitudinal study specific to the skin microbiome of infants and mothers.
“Even at 10 years, the skin microbiome does not look like an adult skin microbiome, based on composition of the ecosystem,” lead author Kimberly A. Capone, PhD, said in an interview during the virtual annual meeting of the American Academy of Dermatology. “The diversity of the microbiome in children’s skin is distinct to that of an adult’s skin. We all have the same bacteria present, but in children it is distributed differently because the bacteria set themselves up based on the nutrients and topography that they find on the skin. Since infant skin is unique to infants, so too is their microbiome when we compare it to adults. It’s been fascinating to observe these children grow and mature, and follow the skin microbiome along this same period.”
During five time points over a period of 10 years, Dr. Capone and her colleagues at the Skillman, N.J.–based Johnson & Johnson Consumer Experience Center, a research and development site, used 16s rRNA gene sequencing to evaluate the skin microbiome on the forearms and foreheads of 30 mothers and their 31 children. The study participants had Fitzpatrick skin types I-IV and the mean age of mothers was 37 years. “We used 16s rRNA gene sequencing for microbiome analysis at the beginning, as that was what was available 10 years ago,” said Dr. Capone, head of the microbiome platform for Johnson & Johnson Consumer Health. “Since then, we continue to use 16s for continuity, but also collected additional swabs for deeper analysis later.”
She and her colleagues often draw samples from the forearm in baby skin clinical studies, “as the arm is a good site to collect relevant data on the body overall,” she explained. “We chose the forearm and forehead specifically here so we can make same body site comparisons to adult sample data which we took from the mothers on the same areas of their body.” Time point 1 was 3 months to 1 year, time point 2 was 2-3 years, time point 3 was 5-6 years, time point 4 was 7-8 years, and time point 5 was 9-10 years.
The researchers found that the skin of infants during the first few weeks of life was similar at age 3 and 4 years. “From that second time point on, we see significant increases in richness and diversity, richness being presence or absence of various bacterial species, and diversity being the relative abundance of those species,” Dr. Capone said. “What you’re basically seeing is that there are new organisms, i.e., richness, coming into the microbiome. We start to detect new ones. Over time, the ecosystem is expanding. It’s evolving because it’s not yet set up.” The evolving skin microbiome on children was dominated by Streptococcus and Staphylococcus. In addition, children had higher levels of Streptococcus, Moraxella, Granulicatella, Gemella and Veillonella, compared with their adult mothers. Adult skin was colonized predominantly by Propionibacterium/Cutibacterium and Staphylococcus.
“The skin microbiome also increased in diversity over time on the forearm, but not face, of the mothers,” Dr. Capone said. “Previous studies have shown how stable the adult skin microbiome is, so it’s intriguing to see the changes that we saw on the mothers in this study.”
The increase in skin microbiome diversity observed in the children is likely due to a variety of factors, she continued, including inherent growth and development, dietary changes, as well as exposure to various environments and other people. “The fact remains that diversity is increasing over time, as the ecosystem evolves,” she said. “Eventually, the skin microbiome will become ‘adultlike’ in puberty, when lipid production increases. This drives increases in Cutibacterium acnes, particularly on the face.”
She acknowledged certain limitations of the study, including its relatively small size and the fact that some of the original subjects did not return for microbiome analysis at later time points. “We need larger cohort studies, additional deeper sequence data, metabolomics and transcriptomics to better understand the function of the skin microbiome over these various ages,” she said.
The study was sponsored by Johnson & Johnson Consumer. Dr. Capone and her two coauthors are employees of the company.
FROM AAD 20
Key clinical point: The skin’s microbial diversity changes with increasing age in children while remaining stable in adult mothers.
Major finding: The skin microbiome in children becomes more diverse between the ages of 3-4 to age 10.
Study details: A longitudinal analysis of 30 mothers and their 31 children.
Disclosures: The study was sponsored by Johnson & Johnson Consumer. Dr. Capone and her two coauthors are employees of the company.
Source: Capone K et al. AAD 20, Abstract F053.
Daily Recap: FDA revokes emergency use of hydroxychloroquine; Hardest hit specialties ranked in financial report
Here are the stories our MDedge editors across specialties think you need to know about today:
It’s official: COVID-19 is bad for your health care business
For the months of March and April 2020, use of medical professional services dropped by 65% and 68%, respectively, compared with last year, and estimated revenue fell by 45% and 48%, FAIR Health, a nonprofit organization that manages a database of 31 billion claim records, said in a new report.
Of the seven specialties included in the study, oral surgery was hit the hardest, followed by gastroenterology, cardiology, orthopedics, dermatology, adult primary care, and pediatric primary care, FAIR Health said.
“Even when medical practices have continued to function via telehealth, many have experienced lower reimbursements for telehealth visits than for in-person visits and more time educating patients on how to use the technology,” according to the report. Read more.
FDA revokes emergency use of hydroxychloroquine
The FDA revoked its decision from March 28 allowing use of hydroxychloroquine and chloroquine to treat people hospitalized with COVID-19 under an emergency use authorization (EUA).
"Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19," the agency announced in a June 15 statement.
"In light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use," noted the FDA. Read more.
Secondary infections common in COVID-19, implications unclear
Secondary respiratory infections appear to be highly prevalent among patients with severe COVID-19, but at this point, most physicians aren’t sure what to make of this understudied phenomenon.
“We really do not understand the implications of secondary infections on outcomes in COVID-19 patients,” David L. Bowton, MD, FCCP, said in an interview. “In most early reports the incidence of secondary infections was much higher in patients dying from COVID-19, compared to survivors, but it isn’t clear whether this indicates that the secondary infection itself led to excess mortality or was more a marker of the severity of the COVID-19 infection."
An early retrospective cohort study including 191 COVID-19 patients in Wuhan, China found that of the 54 who died in hospital, half had secondary bacterial lung infections (Lancet. 2020 Mar 28;395[10229]:1054-62). That comes as no surprise to U.S. physicians, who learned in training that many deaths during the so-called Spanish influenza epidemic were actually caused by secondary pneumonia involving Staphylococcus aureus, commented Daniel L. Ouellette, MD, FCCP. Read more.
Automated insulin delivery system ‘getting better and better’
Medtronic’s next-generation automated insulin delivery system offers significant improvements over the currently available model, particularly in young people with type 1 diabetes, new data suggest.
Data from three trials of such systems using Medtronic’s advanced hybrid closed-loop (AHCL) algorithm (trade name SmartGuard) were presented during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.
Taken together, the data from the three trials showed that the AHCL-based system improved glycemic time-in-range with no increased risk for hypoglycemia, including in children and teenagers, with high patient-reported satisfaction.
“None of these devices is perfect, but they are a substantial improvement over what we’ve had ... They might make the quality of [patient] lives better. That’s really underappreciated,” session moderator Timothy S. Bailey, MD, commented. Read more.
Access more top news from the ADA virtual meeting.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
It’s official: COVID-19 is bad for your health care business
For the months of March and April 2020, use of medical professional services dropped by 65% and 68%, respectively, compared with last year, and estimated revenue fell by 45% and 48%, FAIR Health, a nonprofit organization that manages a database of 31 billion claim records, said in a new report.
Of the seven specialties included in the study, oral surgery was hit the hardest, followed by gastroenterology, cardiology, orthopedics, dermatology, adult primary care, and pediatric primary care, FAIR Health said.
“Even when medical practices have continued to function via telehealth, many have experienced lower reimbursements for telehealth visits than for in-person visits and more time educating patients on how to use the technology,” according to the report. Read more.
FDA revokes emergency use of hydroxychloroquine
The FDA revoked its decision from March 28 allowing use of hydroxychloroquine and chloroquine to treat people hospitalized with COVID-19 under an emergency use authorization (EUA).
"Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19," the agency announced in a June 15 statement.
"In light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use," noted the FDA. Read more.
Secondary infections common in COVID-19, implications unclear
Secondary respiratory infections appear to be highly prevalent among patients with severe COVID-19, but at this point, most physicians aren’t sure what to make of this understudied phenomenon.
“We really do not understand the implications of secondary infections on outcomes in COVID-19 patients,” David L. Bowton, MD, FCCP, said in an interview. “In most early reports the incidence of secondary infections was much higher in patients dying from COVID-19, compared to survivors, but it isn’t clear whether this indicates that the secondary infection itself led to excess mortality or was more a marker of the severity of the COVID-19 infection."
An early retrospective cohort study including 191 COVID-19 patients in Wuhan, China found that of the 54 who died in hospital, half had secondary bacterial lung infections (Lancet. 2020 Mar 28;395[10229]:1054-62). That comes as no surprise to U.S. physicians, who learned in training that many deaths during the so-called Spanish influenza epidemic were actually caused by secondary pneumonia involving Staphylococcus aureus, commented Daniel L. Ouellette, MD, FCCP. Read more.
Automated insulin delivery system ‘getting better and better’
Medtronic’s next-generation automated insulin delivery system offers significant improvements over the currently available model, particularly in young people with type 1 diabetes, new data suggest.
Data from three trials of such systems using Medtronic’s advanced hybrid closed-loop (AHCL) algorithm (trade name SmartGuard) were presented during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.
Taken together, the data from the three trials showed that the AHCL-based system improved glycemic time-in-range with no increased risk for hypoglycemia, including in children and teenagers, with high patient-reported satisfaction.
“None of these devices is perfect, but they are a substantial improvement over what we’ve had ... They might make the quality of [patient] lives better. That’s really underappreciated,” session moderator Timothy S. Bailey, MD, commented. Read more.
Access more top news from the ADA virtual meeting.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
It’s official: COVID-19 is bad for your health care business
For the months of March and April 2020, use of medical professional services dropped by 65% and 68%, respectively, compared with last year, and estimated revenue fell by 45% and 48%, FAIR Health, a nonprofit organization that manages a database of 31 billion claim records, said in a new report.
Of the seven specialties included in the study, oral surgery was hit the hardest, followed by gastroenterology, cardiology, orthopedics, dermatology, adult primary care, and pediatric primary care, FAIR Health said.
“Even when medical practices have continued to function via telehealth, many have experienced lower reimbursements for telehealth visits than for in-person visits and more time educating patients on how to use the technology,” according to the report. Read more.
FDA revokes emergency use of hydroxychloroquine
The FDA revoked its decision from March 28 allowing use of hydroxychloroquine and chloroquine to treat people hospitalized with COVID-19 under an emergency use authorization (EUA).
"Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19," the agency announced in a June 15 statement.
"In light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use," noted the FDA. Read more.
Secondary infections common in COVID-19, implications unclear
Secondary respiratory infections appear to be highly prevalent among patients with severe COVID-19, but at this point, most physicians aren’t sure what to make of this understudied phenomenon.
“We really do not understand the implications of secondary infections on outcomes in COVID-19 patients,” David L. Bowton, MD, FCCP, said in an interview. “In most early reports the incidence of secondary infections was much higher in patients dying from COVID-19, compared to survivors, but it isn’t clear whether this indicates that the secondary infection itself led to excess mortality or was more a marker of the severity of the COVID-19 infection."
An early retrospective cohort study including 191 COVID-19 patients in Wuhan, China found that of the 54 who died in hospital, half had secondary bacterial lung infections (Lancet. 2020 Mar 28;395[10229]:1054-62). That comes as no surprise to U.S. physicians, who learned in training that many deaths during the so-called Spanish influenza epidemic were actually caused by secondary pneumonia involving Staphylococcus aureus, commented Daniel L. Ouellette, MD, FCCP. Read more.
Automated insulin delivery system ‘getting better and better’
Medtronic’s next-generation automated insulin delivery system offers significant improvements over the currently available model, particularly in young people with type 1 diabetes, new data suggest.
Data from three trials of such systems using Medtronic’s advanced hybrid closed-loop (AHCL) algorithm (trade name SmartGuard) were presented during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.
Taken together, the data from the three trials showed that the AHCL-based system improved glycemic time-in-range with no increased risk for hypoglycemia, including in children and teenagers, with high patient-reported satisfaction.
“None of these devices is perfect, but they are a substantial improvement over what we’ve had ... They might make the quality of [patient] lives better. That’s really underappreciated,” session moderator Timothy S. Bailey, MD, commented. Read more.
Access more top news from the ADA virtual meeting.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Be vigilant for scleroderma renal crisis
Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.
“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
Atypical presentations occur in 30%
Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.
While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.
The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.
Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.
“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.
Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.
Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.
Prognosis and predictors
Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.
Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.
“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.
He reported having no financial conflicts regarding his presentation.
Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.
“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
Atypical presentations occur in 30%
Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.
While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.
The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.
Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.
“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.
Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.
Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.
Prognosis and predictors
Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.
Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.
“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.
He reported having no financial conflicts regarding his presentation.
Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.
“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
Atypical presentations occur in 30%
Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.
While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.
The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.
Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.
“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.
Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.
Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.
Prognosis and predictors
Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.
Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.
“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.
He reported having no financial conflicts regarding his presentation.
FROM SOTA 2020
Pediatric Dermatology: A Supplement to Pediatric News & Dermatology News
Content includes:
- Early onset of atopic dermatitis linked to poorer control, could signify more persistent disease
- Patients with actopic dermatitis should be routinely asked about conjunctivitis
- Hope on the horizon: New cantharidin formulation alleviates molluscum contagiosum in pivotal trials
- Patch testing in atopic dermatitis: When and how
- Topical calcineurin inhibitors are an effective treatment option for periorificial dermatitis
- Psychology consults for children’s skin issues can boost adherence, wellness
Content includes:
- Early onset of atopic dermatitis linked to poorer control, could signify more persistent disease
- Patients with actopic dermatitis should be routinely asked about conjunctivitis
- Hope on the horizon: New cantharidin formulation alleviates molluscum contagiosum in pivotal trials
- Patch testing in atopic dermatitis: When and how
- Topical calcineurin inhibitors are an effective treatment option for periorificial dermatitis
- Psychology consults for children’s skin issues can boost adherence, wellness
Content includes:
- Early onset of atopic dermatitis linked to poorer control, could signify more persistent disease
- Patients with actopic dermatitis should be routinely asked about conjunctivitis
- Hope on the horizon: New cantharidin formulation alleviates molluscum contagiosum in pivotal trials
- Patch testing in atopic dermatitis: When and how
- Topical calcineurin inhibitors are an effective treatment option for periorificial dermatitis
- Psychology consults for children’s skin issues can boost adherence, wellness
She Can’t Turn the Other Cheek on the Lesion
ANSWER
The correct answer is seborrheic keratosis (choice “a”).
DISCUSSION
Seborrheic keratosis could not be in the differential because it is, by definition, an epidermal lesion—that is, “stuck on” the surface of the skin. It creates a rough surface that can be easily scraped off. The lesion could have been an actual scar, but other factors (its continuous growth) and the history of excessive ultraviolet exposure pushed us away from including this condition in the differential.
The differential for this patient included sun-caused skin cancers: basal cell carcinoma (BCC; choice “b”), squamous cell carcinoma (SCC; choice “d”), and amelanotic melanoma (choice “c”). These conditions can have a colorless and scar-like appearance, and they also destroy surface adnexae. Therefore, the lack of hairs, pores, or skin lines in a circumscribed area should raise concern for possible skin cancer, especially in at-risk patients such as this one.
BCC (otherwise known as cicatricial basal cell carcinoma) is by far the most common of all sun-caused skin cancers, but it usually presents as an obvious papule or nodule, often with telltale features such as pearly, rolled borders and focal erosion or ulceration. But there are exceptions, and the scar-like BCC is one.
SCC can also occasionally present in this manner, as can amelanotic melanoma, which is a colorless melanoma and very easy to miss. This case perfectly illustrates the point I often make to the students and residents I teach: When skin cancer is suspected, pay at least as much attention to the owner as to the lesion. Also, when in doubt, biopsy will settle the matter.
TREATMENT
For the patient, shave biopsy confirmed the presence of BCC. She was then referred for Mohs micrographic surgery because of the lesion’s size, location, and uncertain visible margins.
ANSWER
The correct answer is seborrheic keratosis (choice “a”).
DISCUSSION
Seborrheic keratosis could not be in the differential because it is, by definition, an epidermal lesion—that is, “stuck on” the surface of the skin. It creates a rough surface that can be easily scraped off. The lesion could have been an actual scar, but other factors (its continuous growth) and the history of excessive ultraviolet exposure pushed us away from including this condition in the differential.
The differential for this patient included sun-caused skin cancers: basal cell carcinoma (BCC; choice “b”), squamous cell carcinoma (SCC; choice “d”), and amelanotic melanoma (choice “c”). These conditions can have a colorless and scar-like appearance, and they also destroy surface adnexae. Therefore, the lack of hairs, pores, or skin lines in a circumscribed area should raise concern for possible skin cancer, especially in at-risk patients such as this one.
BCC (otherwise known as cicatricial basal cell carcinoma) is by far the most common of all sun-caused skin cancers, but it usually presents as an obvious papule or nodule, often with telltale features such as pearly, rolled borders and focal erosion or ulceration. But there are exceptions, and the scar-like BCC is one.
SCC can also occasionally present in this manner, as can amelanotic melanoma, which is a colorless melanoma and very easy to miss. This case perfectly illustrates the point I often make to the students and residents I teach: When skin cancer is suspected, pay at least as much attention to the owner as to the lesion. Also, when in doubt, biopsy will settle the matter.
TREATMENT
For the patient, shave biopsy confirmed the presence of BCC. She was then referred for Mohs micrographic surgery because of the lesion’s size, location, and uncertain visible margins.
ANSWER
The correct answer is seborrheic keratosis (choice “a”).
DISCUSSION
Seborrheic keratosis could not be in the differential because it is, by definition, an epidermal lesion—that is, “stuck on” the surface of the skin. It creates a rough surface that can be easily scraped off. The lesion could have been an actual scar, but other factors (its continuous growth) and the history of excessive ultraviolet exposure pushed us away from including this condition in the differential.
The differential for this patient included sun-caused skin cancers: basal cell carcinoma (BCC; choice “b”), squamous cell carcinoma (SCC; choice “d”), and amelanotic melanoma (choice “c”). These conditions can have a colorless and scar-like appearance, and they also destroy surface adnexae. Therefore, the lack of hairs, pores, or skin lines in a circumscribed area should raise concern for possible skin cancer, especially in at-risk patients such as this one.
BCC (otherwise known as cicatricial basal cell carcinoma) is by far the most common of all sun-caused skin cancers, but it usually presents as an obvious papule or nodule, often with telltale features such as pearly, rolled borders and focal erosion or ulceration. But there are exceptions, and the scar-like BCC is one.
SCC can also occasionally present in this manner, as can amelanotic melanoma, which is a colorless melanoma and very easy to miss. This case perfectly illustrates the point I often make to the students and residents I teach: When skin cancer is suspected, pay at least as much attention to the owner as to the lesion. Also, when in doubt, biopsy will settle the matter.
TREATMENT
For the patient, shave biopsy confirmed the presence of BCC. She was then referred for Mohs micrographic surgery because of the lesion’s size, location, and uncertain visible margins.
For several years, a 70-year-old woman has had an asymptomatic lesion on her cheek that has been growing slowly and steadily. Her primary care provider has reassured her at multiple visits that it should not cause her worry. Still, because of the lesion’s continued growth and her history of excessive sun exposure when she was young, she self-refers to dermatology for evaluation.
The patient has no history of skin cancer but her 2 sisters do, including a recent diagnosis of melanoma for one of them. During the 1950s, the 3 sisters were often outdoors—all burning easily and often and tanning only with difficulty. Since then, the sisters’ sun-drenched days have ended. All are in otherwise excellent health.
Examination reveals a patient with quite fair (type 2) skin and blue eyes. There is abundant evidence of past overexposure to ultraviolet light, including a weathered effect, scattered telangiectasias, and patches of white mottled skin (otherwise known as solar elastosis).
The lesion in question is quite faint and difficult to see. Magnification shows a 2-cm round patch that is slightly lighter than the surrounding skin and completely macular. No induration is felt on palpation, and no nodes are detected in the region.
An even closer and meticulous examination reveals that the surface adnexal structures—such as pores, skin lines, and even tiny hairs—that should be inside the lesion are completely missing. Slightly yellowish discoloration can be seen in the center of the patch. The rest of her skin shows no other worrisome features or lesions.
Upadacitinib looks effective for psoriatic arthritis
Upadacitinib (Rinvoq) improves joint and skin symptoms in patients with psoriatic arthritis for whom at least one other disease-modifying antirheumatic drug (DMARD) didn’t work or wasn’t well tolerated, a pair of phase 3 trials suggests.
“In psoriatic arthritis patients, there’s still a high proportion of patients who do not respond to traditional, nonbiologic DMARDs, so there’s room for improvement,” said Marina Magrey, MD, from the MetroHealth Medical Center, Case Western Reserve University School of Medicine, in Cleveland.
She and her colleagues evaluated the JAK inhibitor, already approved for rheumatoid arthritis in the United States, in the SELECT-PsA 1 and SELECT-PsA 2 trials, which followed more than 2,300 patients with psoriatic arthritis for an average of 6-10 years.
No safety signals emerged for upadacitinib in either trial that weren’t already seen in patients with rheumatoid arthritis, the investigators report, although a lower dose appeared to prompt fewer adverse events.
The research adds upadacitinib “to the armamentarium of medications we have against psoriatic arthritis,” said Dr. Magrey, who is a SELECT-PsA 1 investigator.
“The advantage of this medication is it’s available orally, so the convenience is there. It will enable both patients and physicians to choose from efficacious medications,” she told Medscape Medical News.
The team was “pleasantly surprised by the magnitude and rapidity of effect” of upadacitinib in study participants, said Philip Mease, MD, from the Swedish Medical Center and the University of Washington in Seattle, who is lead investigator for SELECT-PsA 2.
“It’s important to be able to understand if there’s adequate effectiveness in patients who’ve already been around the block several times with other treatments,” Dr. Mease told Medscape Medical News. “This trial demonstrated there was a high degree of effectiveness in each of the clinical domains” of psoriatic arthritis.
Results from both studies were presented at the virtual European League Against Rheumatism 2020 Congress.
SELECT-PsA 1
In SELECT-PsA 1, upadacitinib was compared with adalimumab and placebo in 1705 patients who previously had an inadequate response or intolerance to at least one nonbiologic DMARD. Participants were randomized to receive upadacitinib – 15 mg or 30 mg once daily – adalimumab 40 mg every other week, or placebo.
The primary endpoint was an improvement of at least 20% (ACR20) at week 12.
Secondary endpoints included change in Health Assessment Questionnaire Disability Index (HAQ-DI) score and change in patient assessment of pain on a numeric rating scale from baseline to week 12, achievement of ACR50 and ACR70 at week 12, and achievement of ACR20 at week 2.
Treatment-related adverse events were reported out to week 24 for patients who received at least one dose of upadacitinib.
Improvement in musculoskeletal symptoms, psoriasis, pain, physical function, and fatigue were seen by week 2 in both upadacitinib groups. At week 12, both doses of upadacitinib were noninferior to adalimumab for the achievement of ACR20 (P < .001), and the 30-mg dose was superior to adalimumab (P < .001).
More patients in the upadacitinib groups than in the placebo group met the stringent criteria for disease control, which included the achievement of minimal disease activity, ACR50, and ACR70.
The difference in effectiveness between the two doses of upadacitinib was small, but “there were relatively more adverse events,” such as infections, in the 30-mg group, Dr. Magrey reported, “so 15 mg seems like it will be the dose to go toward FDA approval.”
SELECT-PsA 2
SELECT-PsA 2 compared upadacitinib – 15 mg or 30 mg once daily – with placebo in 641 patients who previously had an inadequate response or intolerance to one or more biologic DMARDs.
The primary endpoint was the achievement of ACR20 at week 12.
Among the many secondary endpoints were a 75% improvement in Psoriasis Area and Severity Index score (PASI 75) at week 16, change in Self-Assessment of Psoriasis Symptoms (SAPS) score from baseline to week 16, the achievement of minimal disease activity at week 24, the achievement of ACR50 and ACR70 at week 12, and the achievement of ACR20 at week 2.
Adverse events were reported for patients who received at least one dose of upadacitinib.
At week 12, ACR20 was achieved by significantly more patients in the 15 mg and 30 mg upadacitinib groups than in the placebo group (56.9% vs. 63.8% vs. 24.1%; P < .0001), as was ACR50 (31.8% vs. 37.6% vs. 4.1%; P < .0001) and ACR70 (8.5% vs. 16.5% vs. 0.5%; P < .0001). In addition, all secondary endpoints were significantly better with upadacitinib than with placebo.
Rates of adverse events were similar in the 15 mg upadacitinib and placebo groups, but the rate was higher in the 30 mg upadacitinib group, including for herpes zoster.
“I was pleasantly surprised by the overall safety profile,” Dr. Mease said. “Yes, you need to pay attention to the potential for infection, but rates of serious infection were very low.”
“We didn’t see opportunistic infections occurring, and the overall adverse-events profile was one where we could be pretty reassuring with patients when introducing the medication and mechanism of action,” he added.
Upadacitinib appears to have significantly improved PASI scores in both trials, which is surprising, said Christopher Ritchlin, MD, from the University of Rochester Medical Center in New York.
“I think the data indicate that upadacitinib is a viable drug for treatment of psoriatic arthritis,” he told Medscape Medical News. “I don’t think it’s going to be tested in psoriasis, but for those with psoriatic arthritis and those whose burden of psoriasis is not particularly elevated, this drug looks like it might be very helpful to practicing physicians and their patients.”
Dr. Ritchlin added that he hopes future research will address whether upadacitinib is effective for axial disease in psoriatic arthritis, which wasn’t measured in these trials.
“I don’t see this as a weakness” of the current research, he said, but “having some spinal measures would be helpful. It’s something additional we’d like to know.”
Both trials were funded by AbbVie. Dr. Magrey reports financial relationships with Amgen, AbbVie, UCB Pharma, Novartis, Eli Lilly, Pfizer, and Janssen. Dr. Mease reports financial relationships with Abbott, Amgen, Biogen, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Genentech, and Janssen. Dr. Ritchlin has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Upadacitinib (Rinvoq) improves joint and skin symptoms in patients with psoriatic arthritis for whom at least one other disease-modifying antirheumatic drug (DMARD) didn’t work or wasn’t well tolerated, a pair of phase 3 trials suggests.
“In psoriatic arthritis patients, there’s still a high proportion of patients who do not respond to traditional, nonbiologic DMARDs, so there’s room for improvement,” said Marina Magrey, MD, from the MetroHealth Medical Center, Case Western Reserve University School of Medicine, in Cleveland.
She and her colleagues evaluated the JAK inhibitor, already approved for rheumatoid arthritis in the United States, in the SELECT-PsA 1 and SELECT-PsA 2 trials, which followed more than 2,300 patients with psoriatic arthritis for an average of 6-10 years.
No safety signals emerged for upadacitinib in either trial that weren’t already seen in patients with rheumatoid arthritis, the investigators report, although a lower dose appeared to prompt fewer adverse events.
The research adds upadacitinib “to the armamentarium of medications we have against psoriatic arthritis,” said Dr. Magrey, who is a SELECT-PsA 1 investigator.
“The advantage of this medication is it’s available orally, so the convenience is there. It will enable both patients and physicians to choose from efficacious medications,” she told Medscape Medical News.
The team was “pleasantly surprised by the magnitude and rapidity of effect” of upadacitinib in study participants, said Philip Mease, MD, from the Swedish Medical Center and the University of Washington in Seattle, who is lead investigator for SELECT-PsA 2.
“It’s important to be able to understand if there’s adequate effectiveness in patients who’ve already been around the block several times with other treatments,” Dr. Mease told Medscape Medical News. “This trial demonstrated there was a high degree of effectiveness in each of the clinical domains” of psoriatic arthritis.
Results from both studies were presented at the virtual European League Against Rheumatism 2020 Congress.
SELECT-PsA 1
In SELECT-PsA 1, upadacitinib was compared with adalimumab and placebo in 1705 patients who previously had an inadequate response or intolerance to at least one nonbiologic DMARD. Participants were randomized to receive upadacitinib – 15 mg or 30 mg once daily – adalimumab 40 mg every other week, or placebo.
The primary endpoint was an improvement of at least 20% (ACR20) at week 12.
Secondary endpoints included change in Health Assessment Questionnaire Disability Index (HAQ-DI) score and change in patient assessment of pain on a numeric rating scale from baseline to week 12, achievement of ACR50 and ACR70 at week 12, and achievement of ACR20 at week 2.
Treatment-related adverse events were reported out to week 24 for patients who received at least one dose of upadacitinib.
Improvement in musculoskeletal symptoms, psoriasis, pain, physical function, and fatigue were seen by week 2 in both upadacitinib groups. At week 12, both doses of upadacitinib were noninferior to adalimumab for the achievement of ACR20 (P < .001), and the 30-mg dose was superior to adalimumab (P < .001).
More patients in the upadacitinib groups than in the placebo group met the stringent criteria for disease control, which included the achievement of minimal disease activity, ACR50, and ACR70.
The difference in effectiveness between the two doses of upadacitinib was small, but “there were relatively more adverse events,” such as infections, in the 30-mg group, Dr. Magrey reported, “so 15 mg seems like it will be the dose to go toward FDA approval.”
SELECT-PsA 2
SELECT-PsA 2 compared upadacitinib – 15 mg or 30 mg once daily – with placebo in 641 patients who previously had an inadequate response or intolerance to one or more biologic DMARDs.
The primary endpoint was the achievement of ACR20 at week 12.
Among the many secondary endpoints were a 75% improvement in Psoriasis Area and Severity Index score (PASI 75) at week 16, change in Self-Assessment of Psoriasis Symptoms (SAPS) score from baseline to week 16, the achievement of minimal disease activity at week 24, the achievement of ACR50 and ACR70 at week 12, and the achievement of ACR20 at week 2.
Adverse events were reported for patients who received at least one dose of upadacitinib.
At week 12, ACR20 was achieved by significantly more patients in the 15 mg and 30 mg upadacitinib groups than in the placebo group (56.9% vs. 63.8% vs. 24.1%; P < .0001), as was ACR50 (31.8% vs. 37.6% vs. 4.1%; P < .0001) and ACR70 (8.5% vs. 16.5% vs. 0.5%; P < .0001). In addition, all secondary endpoints were significantly better with upadacitinib than with placebo.
Rates of adverse events were similar in the 15 mg upadacitinib and placebo groups, but the rate was higher in the 30 mg upadacitinib group, including for herpes zoster.
“I was pleasantly surprised by the overall safety profile,” Dr. Mease said. “Yes, you need to pay attention to the potential for infection, but rates of serious infection were very low.”
“We didn’t see opportunistic infections occurring, and the overall adverse-events profile was one where we could be pretty reassuring with patients when introducing the medication and mechanism of action,” he added.
Upadacitinib appears to have significantly improved PASI scores in both trials, which is surprising, said Christopher Ritchlin, MD, from the University of Rochester Medical Center in New York.
“I think the data indicate that upadacitinib is a viable drug for treatment of psoriatic arthritis,” he told Medscape Medical News. “I don’t think it’s going to be tested in psoriasis, but for those with psoriatic arthritis and those whose burden of psoriasis is not particularly elevated, this drug looks like it might be very helpful to practicing physicians and their patients.”
Dr. Ritchlin added that he hopes future research will address whether upadacitinib is effective for axial disease in psoriatic arthritis, which wasn’t measured in these trials.
“I don’t see this as a weakness” of the current research, he said, but “having some spinal measures would be helpful. It’s something additional we’d like to know.”
Both trials were funded by AbbVie. Dr. Magrey reports financial relationships with Amgen, AbbVie, UCB Pharma, Novartis, Eli Lilly, Pfizer, and Janssen. Dr. Mease reports financial relationships with Abbott, Amgen, Biogen, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Genentech, and Janssen. Dr. Ritchlin has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Upadacitinib (Rinvoq) improves joint and skin symptoms in patients with psoriatic arthritis for whom at least one other disease-modifying antirheumatic drug (DMARD) didn’t work or wasn’t well tolerated, a pair of phase 3 trials suggests.
“In psoriatic arthritis patients, there’s still a high proportion of patients who do not respond to traditional, nonbiologic DMARDs, so there’s room for improvement,” said Marina Magrey, MD, from the MetroHealth Medical Center, Case Western Reserve University School of Medicine, in Cleveland.
She and her colleagues evaluated the JAK inhibitor, already approved for rheumatoid arthritis in the United States, in the SELECT-PsA 1 and SELECT-PsA 2 trials, which followed more than 2,300 patients with psoriatic arthritis for an average of 6-10 years.
No safety signals emerged for upadacitinib in either trial that weren’t already seen in patients with rheumatoid arthritis, the investigators report, although a lower dose appeared to prompt fewer adverse events.
The research adds upadacitinib “to the armamentarium of medications we have against psoriatic arthritis,” said Dr. Magrey, who is a SELECT-PsA 1 investigator.
“The advantage of this medication is it’s available orally, so the convenience is there. It will enable both patients and physicians to choose from efficacious medications,” she told Medscape Medical News.
The team was “pleasantly surprised by the magnitude and rapidity of effect” of upadacitinib in study participants, said Philip Mease, MD, from the Swedish Medical Center and the University of Washington in Seattle, who is lead investigator for SELECT-PsA 2.
“It’s important to be able to understand if there’s adequate effectiveness in patients who’ve already been around the block several times with other treatments,” Dr. Mease told Medscape Medical News. “This trial demonstrated there was a high degree of effectiveness in each of the clinical domains” of psoriatic arthritis.
Results from both studies were presented at the virtual European League Against Rheumatism 2020 Congress.
SELECT-PsA 1
In SELECT-PsA 1, upadacitinib was compared with adalimumab and placebo in 1705 patients who previously had an inadequate response or intolerance to at least one nonbiologic DMARD. Participants were randomized to receive upadacitinib – 15 mg or 30 mg once daily – adalimumab 40 mg every other week, or placebo.
The primary endpoint was an improvement of at least 20% (ACR20) at week 12.
Secondary endpoints included change in Health Assessment Questionnaire Disability Index (HAQ-DI) score and change in patient assessment of pain on a numeric rating scale from baseline to week 12, achievement of ACR50 and ACR70 at week 12, and achievement of ACR20 at week 2.
Treatment-related adverse events were reported out to week 24 for patients who received at least one dose of upadacitinib.
Improvement in musculoskeletal symptoms, psoriasis, pain, physical function, and fatigue were seen by week 2 in both upadacitinib groups. At week 12, both doses of upadacitinib were noninferior to adalimumab for the achievement of ACR20 (P < .001), and the 30-mg dose was superior to adalimumab (P < .001).
More patients in the upadacitinib groups than in the placebo group met the stringent criteria for disease control, which included the achievement of minimal disease activity, ACR50, and ACR70.
The difference in effectiveness between the two doses of upadacitinib was small, but “there were relatively more adverse events,” such as infections, in the 30-mg group, Dr. Magrey reported, “so 15 mg seems like it will be the dose to go toward FDA approval.”
SELECT-PsA 2
SELECT-PsA 2 compared upadacitinib – 15 mg or 30 mg once daily – with placebo in 641 patients who previously had an inadequate response or intolerance to one or more biologic DMARDs.
The primary endpoint was the achievement of ACR20 at week 12.
Among the many secondary endpoints were a 75% improvement in Psoriasis Area and Severity Index score (PASI 75) at week 16, change in Self-Assessment of Psoriasis Symptoms (SAPS) score from baseline to week 16, the achievement of minimal disease activity at week 24, the achievement of ACR50 and ACR70 at week 12, and the achievement of ACR20 at week 2.
Adverse events were reported for patients who received at least one dose of upadacitinib.
At week 12, ACR20 was achieved by significantly more patients in the 15 mg and 30 mg upadacitinib groups than in the placebo group (56.9% vs. 63.8% vs. 24.1%; P < .0001), as was ACR50 (31.8% vs. 37.6% vs. 4.1%; P < .0001) and ACR70 (8.5% vs. 16.5% vs. 0.5%; P < .0001). In addition, all secondary endpoints were significantly better with upadacitinib than with placebo.
Rates of adverse events were similar in the 15 mg upadacitinib and placebo groups, but the rate was higher in the 30 mg upadacitinib group, including for herpes zoster.
“I was pleasantly surprised by the overall safety profile,” Dr. Mease said. “Yes, you need to pay attention to the potential for infection, but rates of serious infection were very low.”
“We didn’t see opportunistic infections occurring, and the overall adverse-events profile was one where we could be pretty reassuring with patients when introducing the medication and mechanism of action,” he added.
Upadacitinib appears to have significantly improved PASI scores in both trials, which is surprising, said Christopher Ritchlin, MD, from the University of Rochester Medical Center in New York.
“I think the data indicate that upadacitinib is a viable drug for treatment of psoriatic arthritis,” he told Medscape Medical News. “I don’t think it’s going to be tested in psoriasis, but for those with psoriatic arthritis and those whose burden of psoriasis is not particularly elevated, this drug looks like it might be very helpful to practicing physicians and their patients.”
Dr. Ritchlin added that he hopes future research will address whether upadacitinib is effective for axial disease in psoriatic arthritis, which wasn’t measured in these trials.
“I don’t see this as a weakness” of the current research, he said, but “having some spinal measures would be helpful. It’s something additional we’d like to know.”
Both trials were funded by AbbVie. Dr. Magrey reports financial relationships with Amgen, AbbVie, UCB Pharma, Novartis, Eli Lilly, Pfizer, and Janssen. Dr. Mease reports financial relationships with Abbott, Amgen, Biogen, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Genentech, and Janssen. Dr. Ritchlin has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Diffuse pustules
The presence of these sterile pustules with an erythematous base led to a diagnosis of acute generalized exanthematous pustulosis (AGEP), also known as a pustular drug eruption. Although pustules are present, AGEP is an allergic response to medications and not an infection.
AGEP can be associated with fever and leukocytosis. Interestingly, antibiotics are a frequent cause—not a treatment—since the pustules are sterile. It also is worth noting, in light of the COVID-19 pandemic, that hydroxychloroquine use has been linked to AGEP, although the number of cases cited in the literature is small.
Treatment is avoidance of the offending medication and symptomatic care. AGEP typically will resolve approximately 2 weeks after discontinuing the medication causing the reaction. Systemic steroids also may be used for treatment in severe cases.
This patient had a history of repeated episodes with his chemotherapy regimen, so he was treated symptomatically with diphenhydramine for the itching. Since chemotherapy was a priority to treat his colon cancer, avoidance of the offending agent was not an option. The Family Medicine Service recommended pretreatment with diphenhydramine 25 to 50 mg orally or intravenously for future rounds of chemotherapy to blunt future responses.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
Mercogliano C, Khan M, Lin C, et al. AGEP overlap induced by hydroxychloroquine: a case report and literature review. J Community Hosp Intern Med Perspect. 2018;8:360-362.
The presence of these sterile pustules with an erythematous base led to a diagnosis of acute generalized exanthematous pustulosis (AGEP), also known as a pustular drug eruption. Although pustules are present, AGEP is an allergic response to medications and not an infection.
AGEP can be associated with fever and leukocytosis. Interestingly, antibiotics are a frequent cause—not a treatment—since the pustules are sterile. It also is worth noting, in light of the COVID-19 pandemic, that hydroxychloroquine use has been linked to AGEP, although the number of cases cited in the literature is small.
Treatment is avoidance of the offending medication and symptomatic care. AGEP typically will resolve approximately 2 weeks after discontinuing the medication causing the reaction. Systemic steroids also may be used for treatment in severe cases.
This patient had a history of repeated episodes with his chemotherapy regimen, so he was treated symptomatically with diphenhydramine for the itching. Since chemotherapy was a priority to treat his colon cancer, avoidance of the offending agent was not an option. The Family Medicine Service recommended pretreatment with diphenhydramine 25 to 50 mg orally or intravenously for future rounds of chemotherapy to blunt future responses.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
The presence of these sterile pustules with an erythematous base led to a diagnosis of acute generalized exanthematous pustulosis (AGEP), also known as a pustular drug eruption. Although pustules are present, AGEP is an allergic response to medications and not an infection.
AGEP can be associated with fever and leukocytosis. Interestingly, antibiotics are a frequent cause—not a treatment—since the pustules are sterile. It also is worth noting, in light of the COVID-19 pandemic, that hydroxychloroquine use has been linked to AGEP, although the number of cases cited in the literature is small.
Treatment is avoidance of the offending medication and symptomatic care. AGEP typically will resolve approximately 2 weeks after discontinuing the medication causing the reaction. Systemic steroids also may be used for treatment in severe cases.
This patient had a history of repeated episodes with his chemotherapy regimen, so he was treated symptomatically with diphenhydramine for the itching. Since chemotherapy was a priority to treat his colon cancer, avoidance of the offending agent was not an option. The Family Medicine Service recommended pretreatment with diphenhydramine 25 to 50 mg orally or intravenously for future rounds of chemotherapy to blunt future responses.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
Mercogliano C, Khan M, Lin C, et al. AGEP overlap induced by hydroxychloroquine: a case report and literature review. J Community Hosp Intern Med Perspect. 2018;8:360-362.
Mercogliano C, Khan M, Lin C, et al. AGEP overlap induced by hydroxychloroquine: a case report and literature review. J Community Hosp Intern Med Perspect. 2018;8:360-362.
