The antifibrinolytic drug tranexamic acid appears to significantly improve quality of life for young women who experience heavy menstrual bleeding, new research suggests.

Writing in the Journal of Pediatric & Adolescent Gynecology, Sarah H. O’Brien, MD, from Nationwide Children’s Hospital and the Ohio State University, both in Columbus, and her coauthors presented the results of an open-label efficacy study of the competitive plasminogen inhibitor in 25 adolescent girls aged 10-19 years who attended pediatric hematology clinics for evaluation or management of heavy menstrual bleeding. The study participants were instructed to take 1,300 mg of tranexamic acid (two tablets) three times a day for up to 5 days during their monthly menstruation for three cycles.

The study found a significant improvement in mean menstrual impact questionnaire (MIQ) scores, which improved from a mean of 3 at baseline to 1.91 (P less than .001). Two-thirds of patients reported at least a one-point improvement from baseline, and all reported that this was clinically meaningful. At baseline, 84% of patients reported heavy to very heavy blood loss, but this decreased to 23% after treatment with tranexamic acid (P less than .001).

The study population included ten individuals (40%) with bleeding disorders. However, the researchers did not see a significant difference in response between those with bleeding disorders and those without.

While the treatment did not significantly affect school attendance (only 24% reported that their heavy bleeding limited school attendance), researchers did see a significant improvement in limitations on physical activities and on social and leisure activities. Patients who reported at baseline that their menstrual bleeding significantly affected their social and leisure activities had an average score improvement of 1.74, a greater than or equal to one point improvement. Participants also reported significant improvements in their Pictorial Blood Assessment Chart scores, which dropped from an average of 255 to 155 (P less than .001).

The treatment did not show any significant effects on hemoglobin or ferritin. The most common adverse events were sinonasal symptoms, such as nasal congestion, headache, and sinus pain, but no thrombotic or ocular adverse events were seen.

Dr. O’Brien and her coauthors wrote that one limitation of their study was using the MIQ score as their primary endpoint as opposed to a more objective measure, such as change in measured blood loss.

“However, a major factor that motivates patients with heavy menstrual bleeding to seek medical care is the negative impact of heavy menstrual bleeding on daily life,” they wrote.

The study drug was supplied by Ferring pharmaceuticals, and the study was supported by the Hemostasis and Thrombosis Research Society. One author disclosed receiving the Joan Fellowship in Pediatric Hemostasis and Thrombosis at Nationwide Children’s Hospital; no other authors said they had relevant financial disclosures.

SOURCE: O’Brien SH et al. J Pediatr Adol Gynec. 2019 Feb 4. doi: 10.1016/j.jpag.2019.01.009.

The antifibrinolytic drug tranexamic acid appears to significantly improve quality of life for young women who experience heavy menstrual bleeding, new research suggests.

Writing in the Journal of Pediatric & Adolescent Gynecology, Sarah H. O’Brien, MD, from Nationwide Children’s Hospital and the Ohio State University, both in Columbus, and her coauthors presented the results of an open-label efficacy study of the competitive plasminogen inhibitor in 25 adolescent girls aged 10-19 years who attended pediatric hematology clinics for evaluation or management of heavy menstrual bleeding. The study participants were instructed to take 1,300 mg of tranexamic acid (two tablets) three times a day for up to 5 days during their monthly menstruation for three cycles.

The study found a significant improvement in mean menstrual impact questionnaire (MIQ) scores, which improved from a mean of 3 at baseline to 1.91 (P less than .001). Two-thirds of patients reported at least a one-point improvement from baseline, and all reported that this was clinically meaningful. At baseline, 84% of patients reported heavy to very heavy blood loss, but this decreased to 23% after treatment with tranexamic acid (P less than .001).

The study population included ten individuals (40%) with bleeding disorders. However, the researchers did not see a significant difference in response between those with bleeding disorders and those without.

While the treatment did not significantly affect school attendance (only 24% reported that their heavy bleeding limited school attendance), researchers did see a significant improvement in limitations on physical activities and on social and leisure activities. Patients who reported at baseline that their menstrual bleeding significantly affected their social and leisure activities had an average score improvement of 1.74, a greater than or equal to one point improvement. Participants also reported significant improvements in their Pictorial Blood Assessment Chart scores, which dropped from an average of 255 to 155 (P less than .001).

The treatment did not show any significant effects on hemoglobin or ferritin. The most common adverse events were sinonasal symptoms, such as nasal congestion, headache, and sinus pain, but no thrombotic or ocular adverse events were seen.

Dr. O’Brien and her coauthors wrote that one limitation of their study was using the MIQ score as their primary endpoint as opposed to a more objective measure, such as change in measured blood loss.

“However, a major factor that motivates patients with heavy menstrual bleeding to seek medical care is the negative impact of heavy menstrual bleeding on daily life,” they wrote.

The study drug was supplied by Ferring pharmaceuticals, and the study was supported by the Hemostasis and Thrombosis Research Society. One author disclosed receiving the Joan Fellowship in Pediatric Hemostasis and Thrombosis at Nationwide Children’s Hospital; no other authors said they had relevant financial disclosures.

SOURCE: O’Brien SH et al. J Pediatr Adol Gynec. 2019 Feb 4. doi: 10.1016/j.jpag.2019.01.009.

The antifibrinolytic drug tranexamic acid appears to significantly improve quality of life for young women who experience heavy menstrual bleeding, new research suggests.

Writing in the Journal of Pediatric & Adolescent Gynecology, Sarah H. O’Brien, MD, from Nationwide Children’s Hospital and the Ohio State University, both in Columbus, and her coauthors presented the results of an open-label efficacy study of the competitive plasminogen inhibitor in 25 adolescent girls aged 10-19 years who attended pediatric hematology clinics for evaluation or management of heavy menstrual bleeding. The study participants were instructed to take 1,300 mg of tranexamic acid (two tablets) three times a day for up to 5 days during their monthly menstruation for three cycles.

The study found a significant improvement in mean menstrual impact questionnaire (MIQ) scores, which improved from a mean of 3 at baseline to 1.91 (P less than .001). Two-thirds of patients reported at least a one-point improvement from baseline, and all reported that this was clinically meaningful. At baseline, 84% of patients reported heavy to very heavy blood loss, but this decreased to 23% after treatment with tranexamic acid (P less than .001).

The study population included ten individuals (40%) with bleeding disorders. However, the researchers did not see a significant difference in response between those with bleeding disorders and those without.

While the treatment did not significantly affect school attendance (only 24% reported that their heavy bleeding limited school attendance), researchers did see a significant improvement in limitations on physical activities and on social and leisure activities. Patients who reported at baseline that their menstrual bleeding significantly affected their social and leisure activities had an average score improvement of 1.74, a greater than or equal to one point improvement. Participants also reported significant improvements in their Pictorial Blood Assessment Chart scores, which dropped from an average of 255 to 155 (P less than .001).

The treatment did not show any significant effects on hemoglobin or ferritin. The most common adverse events were sinonasal symptoms, such as nasal congestion, headache, and sinus pain, but no thrombotic or ocular adverse events were seen.

Dr. O’Brien and her coauthors wrote that one limitation of their study was using the MIQ score as their primary endpoint as opposed to a more objective measure, such as change in measured blood loss.

“However, a major factor that motivates patients with heavy menstrual bleeding to seek medical care is the negative impact of heavy menstrual bleeding on daily life,” they wrote.

The study drug was supplied by Ferring pharmaceuticals, and the study was supported by the Hemostasis and Thrombosis Research Society. One author disclosed receiving the Joan Fellowship in Pediatric Hemostasis and Thrombosis at Nationwide Children’s Hospital; no other authors said they had relevant financial disclosures.

SOURCE: O’Brien SH et al. J Pediatr Adol Gynec. 2019 Feb 4. doi: 10.1016/j.jpag.2019.01.009.

WASHINGTON – Addressing issues related to step therapy and adapting the Stark Law for a value-based care environment are on the Department of Health & Human Service’s agenda this year, according to agency Secretary Alex M. Azar II.

Gregory Twachtman/MDedge News

Speaking Feb. 12 at the American Medical Association’s National Advocacy Conference, Secretary Azar said the agency will be looking into ensuring that patients on medical plans who have found a working drug after going through a step-therapy protocol will not have to restart on a drug that has already failed for them if they switch insurance providers.

“I was very disturbed to hear that stable patients switching among insurance plans, like switching among Medicare Advantage plans, can often be required to start over again on a step therapy regimen,” he said.

“This is not just potentially injurious to their health, it’s also penny-wise and pound-foolish,” Secretary Azar continued. “We know that getting a patient on the right drug, at the right time, is one of the best investments we can make in their health, and we do not want to impede physicians from making that happen. We’re looking at how we can address that issue now.”

The other area Secretary Azar highlighted that the agency is working on is making changes to the Stark Law.

“The Stark Law was written with noble purposes in mind, but it was designed for a fee-for-service system, not the kind of system we are moving toward today,” he said. “We’ve heard from many, many stakeholders, including the AMA, about the need to update the enumerated exceptions in the Stark Law to include value-based approaches to care.”

He added that how care coordination interacts with the antikickback statutes and HIPAA are also going to be examined.

Secretary Azar did not offer any timelines or other more specific details about how the agency plans to tackle these issues.

He used most of his speech to discuss recent regulatory actions around drug pricing and pushed for support for the Part B drug pricing model that the agency is preparing for a formal proposed rule, despite having received a critical reception from medical societies.

“If you have a small practice that uses infusions, and you don’t want to bear the risk of buy and bill, now you’re off the hook,” he said. “We’ll allow you to work with private vendors who can take the risk for buying the drugs in a way that isn’t possible today. But if you’re part of a much larger practice that’s able to drive a better deal than you could on your own, or want to band together with other practices to do the purchasing, then you can do that, too.”

He continued: “Next is the launch of the actual proposed rule, followed by the rule itself, which, I’ll remind you, is just a model.”

However, despite it being a model under test from the Center for Medicare & Medicaid Innovation, the advanced notice of proposed rule making that was issued in October 2018 suggested that participation in the so-called International Pricing Index model would be mandatory.

Secretary Azar did not acknowledge any mandatory participation in his pitch for support, noting that CMMI models “are carefully assessed. We will closely monitor how the model will affect clinical outcomes, including patients’ adherence to their drugs. We believe that the lower costs will, of course, mean better patient access to drugs, better adherence, and better outcomes for the care you provide. That is the goal.”

[email protected]

WASHINGTON – Addressing issues related to step therapy and adapting the Stark Law for a value-based care environment are on the Department of Health & Human Service’s agenda this year, according to agency Secretary Alex M. Azar II.

Gregory Twachtman/MDedge News

Speaking Feb. 12 at the American Medical Association’s National Advocacy Conference, Secretary Azar said the agency will be looking into ensuring that patients on medical plans who have found a working drug after going through a step-therapy protocol will not have to restart on a drug that has already failed for them if they switch insurance providers.

“I was very disturbed to hear that stable patients switching among insurance plans, like switching among Medicare Advantage plans, can often be required to start over again on a step therapy regimen,” he said.

“This is not just potentially injurious to their health, it’s also penny-wise and pound-foolish,” Secretary Azar continued. “We know that getting a patient on the right drug, at the right time, is one of the best investments we can make in their health, and we do not want to impede physicians from making that happen. We’re looking at how we can address that issue now.”

The other area Secretary Azar highlighted that the agency is working on is making changes to the Stark Law.

“The Stark Law was written with noble purposes in mind, but it was designed for a fee-for-service system, not the kind of system we are moving toward today,” he said. “We’ve heard from many, many stakeholders, including the AMA, about the need to update the enumerated exceptions in the Stark Law to include value-based approaches to care.”

He added that how care coordination interacts with the antikickback statutes and HIPAA are also going to be examined.

Secretary Azar did not offer any timelines or other more specific details about how the agency plans to tackle these issues.

He used most of his speech to discuss recent regulatory actions around drug pricing and pushed for support for the Part B drug pricing model that the agency is preparing for a formal proposed rule, despite having received a critical reception from medical societies.

“If you have a small practice that uses infusions, and you don’t want to bear the risk of buy and bill, now you’re off the hook,” he said. “We’ll allow you to work with private vendors who can take the risk for buying the drugs in a way that isn’t possible today. But if you’re part of a much larger practice that’s able to drive a better deal than you could on your own, or want to band together with other practices to do the purchasing, then you can do that, too.”

He continued: “Next is the launch of the actual proposed rule, followed by the rule itself, which, I’ll remind you, is just a model.”

However, despite it being a model under test from the Center for Medicare & Medicaid Innovation, the advanced notice of proposed rule making that was issued in October 2018 suggested that participation in the so-called International Pricing Index model would be mandatory.

Secretary Azar did not acknowledge any mandatory participation in his pitch for support, noting that CMMI models “are carefully assessed. We will closely monitor how the model will affect clinical outcomes, including patients’ adherence to their drugs. We believe that the lower costs will, of course, mean better patient access to drugs, better adherence, and better outcomes for the care you provide. That is the goal.”

[email protected]

WASHINGTON – Addressing issues related to step therapy and adapting the Stark Law for a value-based care environment are on the Department of Health & Human Service’s agenda this year, according to agency Secretary Alex M. Azar II.

Gregory Twachtman/MDedge News

Speaking Feb. 12 at the American Medical Association’s National Advocacy Conference, Secretary Azar said the agency will be looking into ensuring that patients on medical plans who have found a working drug after going through a step-therapy protocol will not have to restart on a drug that has already failed for them if they switch insurance providers.

“I was very disturbed to hear that stable patients switching among insurance plans, like switching among Medicare Advantage plans, can often be required to start over again on a step therapy regimen,” he said.

“This is not just potentially injurious to their health, it’s also penny-wise and pound-foolish,” Secretary Azar continued. “We know that getting a patient on the right drug, at the right time, is one of the best investments we can make in their health, and we do not want to impede physicians from making that happen. We’re looking at how we can address that issue now.”

The other area Secretary Azar highlighted that the agency is working on is making changes to the Stark Law.

“The Stark Law was written with noble purposes in mind, but it was designed for a fee-for-service system, not the kind of system we are moving toward today,” he said. “We’ve heard from many, many stakeholders, including the AMA, about the need to update the enumerated exceptions in the Stark Law to include value-based approaches to care.”

He added that how care coordination interacts with the antikickback statutes and HIPAA are also going to be examined.

Secretary Azar did not offer any timelines or other more specific details about how the agency plans to tackle these issues.

He used most of his speech to discuss recent regulatory actions around drug pricing and pushed for support for the Part B drug pricing model that the agency is preparing for a formal proposed rule, despite having received a critical reception from medical societies.

“If you have a small practice that uses infusions, and you don’t want to bear the risk of buy and bill, now you’re off the hook,” he said. “We’ll allow you to work with private vendors who can take the risk for buying the drugs in a way that isn’t possible today. But if you’re part of a much larger practice that’s able to drive a better deal than you could on your own, or want to band together with other practices to do the purchasing, then you can do that, too.”

He continued: “Next is the launch of the actual proposed rule, followed by the rule itself, which, I’ll remind you, is just a model.”

However, despite it being a model under test from the Center for Medicare & Medicaid Innovation, the advanced notice of proposed rule making that was issued in October 2018 suggested that participation in the so-called International Pricing Index model would be mandatory.

Secretary Azar did not acknowledge any mandatory participation in his pitch for support, noting that CMMI models “are carefully assessed. We will closely monitor how the model will affect clinical outcomes, including patients’ adherence to their drugs. We believe that the lower costs will, of course, mean better patient access to drugs, better adherence, and better outcomes for the care you provide. That is the goal.”

[email protected]

A decade ago, I gave my senior expert talk at the University of California, San Francisco, department of dermatology on skin care and brought up the controversial topic that sterile or clean skin is bad. At the time, I initiated the conversation on the microbiome and the importance of good bacteria in preserving the epidermal barrier of the skin, particularly with conditions such as atopic dermatitis. Today, I not only preach this message to my patients, but I also practice the “less-is-more” philosophy every day. It is my hope that this brief summary of the skin microbiome and the importance of skin bacteria will affect the development of the next generation of skin care products.

The normal human skin is a microbiome colonized by 10,000-1,000,000 bacteria units/cm² that prevent the growth of pathogenic organisms and maintain the immunity of the skin. The diversity and type of skin bacteria (that is, Staphylococcus or Propionibacterium acnes), as well as their concentration, varies by person, body location, and environment. Symbiotic with bacteria on the skin are yeasts, such as Malassezia, and parasites, such as Demodex. When the composition and diversity of microorganisms are disrupted, the skin can no longer protect its barrier functions, leading to pathogenic bacterial infections, altered skin pH, decreased production of antimicrobial peptides, and increased inflammation. The microbiome also serves to shield the skin from environmental stressors, such as free radicals, UV radiation, and pollution.

What can lead to disruption of our skin is hygiene. Over-washing; stripping of the skin with lathering cleaner; overexfoliation; long, hot showers; and the use of products with antibacterial properties have increased over the last 50 years, and so has skin disease. The removal of these microorganisms, either by overcleansing or with antibiotic use, disrupts the microflora and leads to pH-imbalanced and inflamed skin. Our microflora contains prebiotics, probiotics, and postbiotics. Prebiotics are the “fertilizer” or “food,” so to speak, that encourages these essential microorganisms to grow; probiotics are the microorganisms themselves; and postbiotics are the chemical byproducts of bacteria, such as antimicrobial peptides and fragments of dead bacterial cells that remain on the skin.

Skin care tailored to our unique microbiome is in its infancy. On the frontier of microflora-rich skin care are organisms like Bifidobacterium longum, which increases the skin’s resistance to temperature and product-related irritation. Streptococcus thermophilus has been shown to increase the production of ceramides in the skin, which could help atopic dermatitis. Lactobacillus paracasei has been shown to inhibit the neuropeptide substance P, which increases inflammation and oil production. Enterococcus faecalis, Streptococcus salivarius, and Lactobacillus plantarum have all been shown to decrease Propionibacterium acnes. Bacillus coagulans and Bifidobacterium breve have been shown to decrease free radicals and protect against UV rays.


Probiotic, prebiotic, and postbiotic skin care, however, does have its challenges. Probiotics are live bacteria, and thus need refrigeration. These products are also not intended for use in anyone who is immunosuppressed or neutropenic. Another complexity in the development of probiotic, prebiotic, and postbiotic skin care is that each person may have a different need in terms of their skin microflora and that microflora is inherently different in different body parts. Furthermore, people with skin inflammation may require a different concentration or population of that flora.

Darryl Leja, NHGRI

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

References

Al-Ghazzewi F et al. Benef Microbes. 2014 Jun 1;5(2):99-107.

Baquerizo Nole K et al. J Am Acad Dermatol. 2014 Oct;71(4):814-21.

Chen Y et al. J Am Acad Dermatol. 2013 Jul;69(1):143-55.e3.

Grice E et al. Nat Rev Microbiol. 2011 Apr;9(4):244-53.

Kong H et al. J Invest Dermatol. 2012 Mar;132(3, part 2):933-9.

Hutkins R et al. Curr Opin Biotechnol. 2016 Feb;37:1-7.

Kober MM et al. Int J Womens Dermatol. 2015 Apr 6;1(2):85-9.

Maquire M. et al. Arch Dermatol Res. 2017 Aug;309(6):411-421.

Sugimoto S. et al. Photodermatol. Photoimmunol. Photomed. 2012 Dec;28(6): 312-9.
 

A decade ago, I gave my senior expert talk at the University of California, San Francisco, department of dermatology on skin care and brought up the controversial topic that sterile or clean skin is bad. At the time, I initiated the conversation on the microbiome and the importance of good bacteria in preserving the epidermal barrier of the skin, particularly with conditions such as atopic dermatitis. Today, I not only preach this message to my patients, but I also practice the “less-is-more” philosophy every day. It is my hope that this brief summary of the skin microbiome and the importance of skin bacteria will affect the development of the next generation of skin care products.

The normal human skin is a microbiome colonized by 10,000-1,000,000 bacteria units/cm² that prevent the growth of pathogenic organisms and maintain the immunity of the skin. The diversity and type of skin bacteria (that is, Staphylococcus or Propionibacterium acnes), as well as their concentration, varies by person, body location, and environment. Symbiotic with bacteria on the skin are yeasts, such as Malassezia, and parasites, such as Demodex. When the composition and diversity of microorganisms are disrupted, the skin can no longer protect its barrier functions, leading to pathogenic bacterial infections, altered skin pH, decreased production of antimicrobial peptides, and increased inflammation. The microbiome also serves to shield the skin from environmental stressors, such as free radicals, UV radiation, and pollution.

What can lead to disruption of our skin is hygiene. Over-washing; stripping of the skin with lathering cleaner; overexfoliation; long, hot showers; and the use of products with antibacterial properties have increased over the last 50 years, and so has skin disease. The removal of these microorganisms, either by overcleansing or with antibiotic use, disrupts the microflora and leads to pH-imbalanced and inflamed skin. Our microflora contains prebiotics, probiotics, and postbiotics. Prebiotics are the “fertilizer” or “food,” so to speak, that encourages these essential microorganisms to grow; probiotics are the microorganisms themselves; and postbiotics are the chemical byproducts of bacteria, such as antimicrobial peptides and fragments of dead bacterial cells that remain on the skin.

Skin care tailored to our unique microbiome is in its infancy. On the frontier of microflora-rich skin care are organisms like Bifidobacterium longum, which increases the skin’s resistance to temperature and product-related irritation. Streptococcus thermophilus has been shown to increase the production of ceramides in the skin, which could help atopic dermatitis. Lactobacillus paracasei has been shown to inhibit the neuropeptide substance P, which increases inflammation and oil production. Enterococcus faecalis, Streptococcus salivarius, and Lactobacillus plantarum have all been shown to decrease Propionibacterium acnes. Bacillus coagulans and Bifidobacterium breve have been shown to decrease free radicals and protect against UV rays.


Probiotic, prebiotic, and postbiotic skin care, however, does have its challenges. Probiotics are live bacteria, and thus need refrigeration. These products are also not intended for use in anyone who is immunosuppressed or neutropenic. Another complexity in the development of probiotic, prebiotic, and postbiotic skin care is that each person may have a different need in terms of their skin microflora and that microflora is inherently different in different body parts. Furthermore, people with skin inflammation may require a different concentration or population of that flora.

Darryl Leja, NHGRI

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

References

Al-Ghazzewi F et al. Benef Microbes. 2014 Jun 1;5(2):99-107.

Baquerizo Nole K et al. J Am Acad Dermatol. 2014 Oct;71(4):814-21.

Chen Y et al. J Am Acad Dermatol. 2013 Jul;69(1):143-55.e3.

Grice E et al. Nat Rev Microbiol. 2011 Apr;9(4):244-53.

Kong H et al. J Invest Dermatol. 2012 Mar;132(3, part 2):933-9.

Hutkins R et al. Curr Opin Biotechnol. 2016 Feb;37:1-7.

Kober MM et al. Int J Womens Dermatol. 2015 Apr 6;1(2):85-9.

Maquire M. et al. Arch Dermatol Res. 2017 Aug;309(6):411-421.

Sugimoto S. et al. Photodermatol. Photoimmunol. Photomed. 2012 Dec;28(6): 312-9.
 

A decade ago, I gave my senior expert talk at the University of California, San Francisco, department of dermatology on skin care and brought up the controversial topic that sterile or clean skin is bad. At the time, I initiated the conversation on the microbiome and the importance of good bacteria in preserving the epidermal barrier of the skin, particularly with conditions such as atopic dermatitis. Today, I not only preach this message to my patients, but I also practice the “less-is-more” philosophy every day. It is my hope that this brief summary of the skin microbiome and the importance of skin bacteria will affect the development of the next generation of skin care products.

The normal human skin is a microbiome colonized by 10,000-1,000,000 bacteria units/cm² that prevent the growth of pathogenic organisms and maintain the immunity of the skin. The diversity and type of skin bacteria (that is, Staphylococcus or Propionibacterium acnes), as well as their concentration, varies by person, body location, and environment. Symbiotic with bacteria on the skin are yeasts, such as Malassezia, and parasites, such as Demodex. When the composition and diversity of microorganisms are disrupted, the skin can no longer protect its barrier functions, leading to pathogenic bacterial infections, altered skin pH, decreased production of antimicrobial peptides, and increased inflammation. The microbiome also serves to shield the skin from environmental stressors, such as free radicals, UV radiation, and pollution.

What can lead to disruption of our skin is hygiene. Over-washing; stripping of the skin with lathering cleaner; overexfoliation; long, hot showers; and the use of products with antibacterial properties have increased over the last 50 years, and so has skin disease. The removal of these microorganisms, either by overcleansing or with antibiotic use, disrupts the microflora and leads to pH-imbalanced and inflamed skin. Our microflora contains prebiotics, probiotics, and postbiotics. Prebiotics are the “fertilizer” or “food,” so to speak, that encourages these essential microorganisms to grow; probiotics are the microorganisms themselves; and postbiotics are the chemical byproducts of bacteria, such as antimicrobial peptides and fragments of dead bacterial cells that remain on the skin.

Skin care tailored to our unique microbiome is in its infancy. On the frontier of microflora-rich skin care are organisms like Bifidobacterium longum, which increases the skin’s resistance to temperature and product-related irritation. Streptococcus thermophilus has been shown to increase the production of ceramides in the skin, which could help atopic dermatitis. Lactobacillus paracasei has been shown to inhibit the neuropeptide substance P, which increases inflammation and oil production. Enterococcus faecalis, Streptococcus salivarius, and Lactobacillus plantarum have all been shown to decrease Propionibacterium acnes. Bacillus coagulans and Bifidobacterium breve have been shown to decrease free radicals and protect against UV rays.


Probiotic, prebiotic, and postbiotic skin care, however, does have its challenges. Probiotics are live bacteria, and thus need refrigeration. These products are also not intended for use in anyone who is immunosuppressed or neutropenic. Another complexity in the development of probiotic, prebiotic, and postbiotic skin care is that each person may have a different need in terms of their skin microflora and that microflora is inherently different in different body parts. Furthermore, people with skin inflammation may require a different concentration or population of that flora.

Darryl Leja, NHGRI

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

References

Al-Ghazzewi F et al. Benef Microbes. 2014 Jun 1;5(2):99-107.

Baquerizo Nole K et al. J Am Acad Dermatol. 2014 Oct;71(4):814-21.

Chen Y et al. J Am Acad Dermatol. 2013 Jul;69(1):143-55.e3.

Grice E et al. Nat Rev Microbiol. 2011 Apr;9(4):244-53.

Kong H et al. J Invest Dermatol. 2012 Mar;132(3, part 2):933-9.

Hutkins R et al. Curr Opin Biotechnol. 2016 Feb;37:1-7.

Kober MM et al. Int J Womens Dermatol. 2015 Apr 6;1(2):85-9.

Maquire M. et al. Arch Dermatol Res. 2017 Aug;309(6):411-421.

Sugimoto S. et al. Photodermatol. Photoimmunol. Photomed. 2012 Dec;28(6): 312-9.
 

Patients with the aggressive skin cancer Merkel cell carcinoma who were treated with the immune checkpoint inhibitor pembrolizumab (Keytruda) in the first line had higher complete response rates, better progression-free survival, and longer overall survival than historical controls treated with cytotoxic chemotherapy.

Among 50 adults with advanced Merkel cell carcinoma (MCC) with no prior systemic therapy who received pembrolizumab 2 mg/kg every 3 weeks for up to 2 years in a phase 2 clinical trial (NCT02267603), 24% had a complete response and 32% a partial response, for an overall response rate of 56%.

The 24-month overall survival rate was 68.7%, with median overall survival not reached after a median follow-up time of 14.9 months. In contrast, a retrospective study of 67 patients with MCC treated with first-line chemotherapy showed an ORR of 29.4%, a median OS of 10.5 months, and a 24-month OS of 24.5% (Future Oncol. 2017 Aug;13(19):1699-1710).

Similarly, a second retrospective study showed that, among 62 patients treated with first-line chemotherapy, the ORR was 55%, median OS was 9.5 months, and 24-month OS was 20% (Cancer Med. 2016 Sep;5(9):2294-2301), reported Paul Nghiem, MD, PhD, from the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, and his colleagues.

The rationale for using a checkpoint inhibitor for advanced MCC is that “[m]ultiple lines of evidence support the notion that MCC is an immunogenic cancer, including the fact that MCC incidence is greater than 10-fold higher in chronically immunosuppressed persons,” they wrote in the Journal of Clinical Oncology.

The current National Comprehensive Cancer Network guideline on Merkel cell carcinoma recommends the use of the programmed death–1/programmed death–ligand 1 (PD-1/PD-L1) inhibitors pembrolizumab, avelumab (Bavencio), or nivolumab (Opdivo) as preferred first-line systemic therapy for patients with disseminated disease, Dr. Nghiem and his colleagues noted.

In the current report, they presented data on the longest follow-up to date of patients with advance MCC who received a PD-1 inhibitor in the first line.

In the multicenter, phase 2 trial, 50 patients with a median age of 70.5 years were treated. Of this group, 64% had tumors positive for the Merkel cell polyomavirus and 49% had PD-L1 expression on tumor cells.

Of the 50 total patients, 28 had an objective response according to Response Evaluation Criteria in Solid Tumors version 1.1, including 12 with a complete response and 16 with a partial response. A total of 5 patients had stable disease, 16 had progressive disease, and 1 patient died before the first on-treatment scan for assessment.

After a median follow-up of 4.9 months, the 24-month progression-free survival rate (PFS) was 48.3% months, with a median PFS of 16.8 months.

As noted before, the 24-month OS rate was 68.7% and the median OS had not been reached at the time of the analysis.

There were no significant differences in PFS or OS between patients with tumors positive or negative for the Merkel polyomavirus, and there was a nonsignificant trend toward better PFS and OS for patients whose tumors had PD-L1 expression greater than 1%.

In all, 48 of the 50 patients had a treatment-related adverse event of any kind, and 14 had grade 3 or greater events. Treatment-related events led to discontinuation of pembrolizumab for seven patients, and one patient, a 73-year-old man with metastatic MCC and atrial fibrillation, developed pericardial and pleural effusions 1 day after receiving a single pembrolizumab infusion. The patient died 10 days after receiving pembrolizumab, and his death was deemed to be related to the drug.

The investigators noted that the drug’s efficacy in patients with both polyomavirus- and UV-induced subtypes of MCC “provides compelling evidence that both the quality and quantity of tumor antigens are important factors driving antitumor immunity and tumor rejection.”

The study was supported by grants from the National Cancer Institute, the Merkel cell carcinoma (MCC) patient gift fund at University of Washington, the Kelsey Dickson MCC Challenge Grant from the Prostate Cancer Foundation, and Merck, which provided pembrolizumab and partial funding. Dr. Nghiem reported receiving honoraria, travel expenses, and a consulting or advisory role from/for Merck and others. Multiple coauthors reported similar relations with Merck and/or other companies.

SOURCE: Nghiem P et al. J Clin Oncol. 2019 Feb 6. doi: 10.1200/JCO.18.01896.

Patients with the aggressive skin cancer Merkel cell carcinoma who were treated with the immune checkpoint inhibitor pembrolizumab (Keytruda) in the first line had higher complete response rates, better progression-free survival, and longer overall survival than historical controls treated with cytotoxic chemotherapy.

Among 50 adults with advanced Merkel cell carcinoma (MCC) with no prior systemic therapy who received pembrolizumab 2 mg/kg every 3 weeks for up to 2 years in a phase 2 clinical trial (NCT02267603), 24% had a complete response and 32% a partial response, for an overall response rate of 56%.

The 24-month overall survival rate was 68.7%, with median overall survival not reached after a median follow-up time of 14.9 months. In contrast, a retrospective study of 67 patients with MCC treated with first-line chemotherapy showed an ORR of 29.4%, a median OS of 10.5 months, and a 24-month OS of 24.5% (Future Oncol. 2017 Aug;13(19):1699-1710).

Similarly, a second retrospective study showed that, among 62 patients treated with first-line chemotherapy, the ORR was 55%, median OS was 9.5 months, and 24-month OS was 20% (Cancer Med. 2016 Sep;5(9):2294-2301), reported Paul Nghiem, MD, PhD, from the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, and his colleagues.

The rationale for using a checkpoint inhibitor for advanced MCC is that “[m]ultiple lines of evidence support the notion that MCC is an immunogenic cancer, including the fact that MCC incidence is greater than 10-fold higher in chronically immunosuppressed persons,” they wrote in the Journal of Clinical Oncology.

The current National Comprehensive Cancer Network guideline on Merkel cell carcinoma recommends the use of the programmed death–1/programmed death–ligand 1 (PD-1/PD-L1) inhibitors pembrolizumab, avelumab (Bavencio), or nivolumab (Opdivo) as preferred first-line systemic therapy for patients with disseminated disease, Dr. Nghiem and his colleagues noted.

In the current report, they presented data on the longest follow-up to date of patients with advance MCC who received a PD-1 inhibitor in the first line.

In the multicenter, phase 2 trial, 50 patients with a median age of 70.5 years were treated. Of this group, 64% had tumors positive for the Merkel cell polyomavirus and 49% had PD-L1 expression on tumor cells.

Of the 50 total patients, 28 had an objective response according to Response Evaluation Criteria in Solid Tumors version 1.1, including 12 with a complete response and 16 with a partial response. A total of 5 patients had stable disease, 16 had progressive disease, and 1 patient died before the first on-treatment scan for assessment.

After a median follow-up of 4.9 months, the 24-month progression-free survival rate (PFS) was 48.3% months, with a median PFS of 16.8 months.

As noted before, the 24-month OS rate was 68.7% and the median OS had not been reached at the time of the analysis.

There were no significant differences in PFS or OS between patients with tumors positive or negative for the Merkel polyomavirus, and there was a nonsignificant trend toward better PFS and OS for patients whose tumors had PD-L1 expression greater than 1%.

In all, 48 of the 50 patients had a treatment-related adverse event of any kind, and 14 had grade 3 or greater events. Treatment-related events led to discontinuation of pembrolizumab for seven patients, and one patient, a 73-year-old man with metastatic MCC and atrial fibrillation, developed pericardial and pleural effusions 1 day after receiving a single pembrolizumab infusion. The patient died 10 days after receiving pembrolizumab, and his death was deemed to be related to the drug.

The investigators noted that the drug’s efficacy in patients with both polyomavirus- and UV-induced subtypes of MCC “provides compelling evidence that both the quality and quantity of tumor antigens are important factors driving antitumor immunity and tumor rejection.”

The study was supported by grants from the National Cancer Institute, the Merkel cell carcinoma (MCC) patient gift fund at University of Washington, the Kelsey Dickson MCC Challenge Grant from the Prostate Cancer Foundation, and Merck, which provided pembrolizumab and partial funding. Dr. Nghiem reported receiving honoraria, travel expenses, and a consulting or advisory role from/for Merck and others. Multiple coauthors reported similar relations with Merck and/or other companies.

SOURCE: Nghiem P et al. J Clin Oncol. 2019 Feb 6. doi: 10.1200/JCO.18.01896.

Patients with the aggressive skin cancer Merkel cell carcinoma who were treated with the immune checkpoint inhibitor pembrolizumab (Keytruda) in the first line had higher complete response rates, better progression-free survival, and longer overall survival than historical controls treated with cytotoxic chemotherapy.

Among 50 adults with advanced Merkel cell carcinoma (MCC) with no prior systemic therapy who received pembrolizumab 2 mg/kg every 3 weeks for up to 2 years in a phase 2 clinical trial (NCT02267603), 24% had a complete response and 32% a partial response, for an overall response rate of 56%.

The 24-month overall survival rate was 68.7%, with median overall survival not reached after a median follow-up time of 14.9 months. In contrast, a retrospective study of 67 patients with MCC treated with first-line chemotherapy showed an ORR of 29.4%, a median OS of 10.5 months, and a 24-month OS of 24.5% (Future Oncol. 2017 Aug;13(19):1699-1710).

Similarly, a second retrospective study showed that, among 62 patients treated with first-line chemotherapy, the ORR was 55%, median OS was 9.5 months, and 24-month OS was 20% (Cancer Med. 2016 Sep;5(9):2294-2301), reported Paul Nghiem, MD, PhD, from the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, and his colleagues.

The rationale for using a checkpoint inhibitor for advanced MCC is that “[m]ultiple lines of evidence support the notion that MCC is an immunogenic cancer, including the fact that MCC incidence is greater than 10-fold higher in chronically immunosuppressed persons,” they wrote in the Journal of Clinical Oncology.

The current National Comprehensive Cancer Network guideline on Merkel cell carcinoma recommends the use of the programmed death–1/programmed death–ligand 1 (PD-1/PD-L1) inhibitors pembrolizumab, avelumab (Bavencio), or nivolumab (Opdivo) as preferred first-line systemic therapy for patients with disseminated disease, Dr. Nghiem and his colleagues noted.

In the current report, they presented data on the longest follow-up to date of patients with advance MCC who received a PD-1 inhibitor in the first line.

In the multicenter, phase 2 trial, 50 patients with a median age of 70.5 years were treated. Of this group, 64% had tumors positive for the Merkel cell polyomavirus and 49% had PD-L1 expression on tumor cells.

Of the 50 total patients, 28 had an objective response according to Response Evaluation Criteria in Solid Tumors version 1.1, including 12 with a complete response and 16 with a partial response. A total of 5 patients had stable disease, 16 had progressive disease, and 1 patient died before the first on-treatment scan for assessment.

After a median follow-up of 4.9 months, the 24-month progression-free survival rate (PFS) was 48.3% months, with a median PFS of 16.8 months.

As noted before, the 24-month OS rate was 68.7% and the median OS had not been reached at the time of the analysis.

There were no significant differences in PFS or OS between patients with tumors positive or negative for the Merkel polyomavirus, and there was a nonsignificant trend toward better PFS and OS for patients whose tumors had PD-L1 expression greater than 1%.

In all, 48 of the 50 patients had a treatment-related adverse event of any kind, and 14 had grade 3 or greater events. Treatment-related events led to discontinuation of pembrolizumab for seven patients, and one patient, a 73-year-old man with metastatic MCC and atrial fibrillation, developed pericardial and pleural effusions 1 day after receiving a single pembrolizumab infusion. The patient died 10 days after receiving pembrolizumab, and his death was deemed to be related to the drug.

The investigators noted that the drug’s efficacy in patients with both polyomavirus- and UV-induced subtypes of MCC “provides compelling evidence that both the quality and quantity of tumor antigens are important factors driving antitumor immunity and tumor rejection.”

The study was supported by grants from the National Cancer Institute, the Merkel cell carcinoma (MCC) patient gift fund at University of Washington, the Kelsey Dickson MCC Challenge Grant from the Prostate Cancer Foundation, and Merck, which provided pembrolizumab and partial funding. Dr. Nghiem reported receiving honoraria, travel expenses, and a consulting or advisory role from/for Merck and others. Multiple coauthors reported similar relations with Merck and/or other companies.

SOURCE: Nghiem P et al. J Clin Oncol. 2019 Feb 6. doi: 10.1200/JCO.18.01896.

The Food and Drug Administration has approved a split-dosing regimen for daratumumab (Darzalex) in patients with multiple myeloma, allowing the first infusion to be split over 2 days.

FDA approval is based on results from the global, multi-arm, phase 1b EQUULEUS (MMY1001) trial, which evaluated daratumumab in combination with a variety of treatment regimens. Splitting the first infusion over 2 consecutive days reduced the duration of the infusion and resulted in a similar rate of infusion site reactions; concentrations were similar at the end of weekly dosing in patients who received the first infusion at once or over a 2-day period.

The adverse events reported in EQUULEUS (MMY1001) were largely similar to those seen in previous trials; the most common adverse events include infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, constipation, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy, and upper respiratory tract infection.

The approval providers “added flexibility for how patients may receive initial treatment,” Craig Tendler, MD, vice president of clinical development and global medical affairs at Janssen Research & Development, said in a statement.

[email protected]

The Food and Drug Administration has approved a split-dosing regimen for daratumumab (Darzalex) in patients with multiple myeloma, allowing the first infusion to be split over 2 days.

FDA approval is based on results from the global, multi-arm, phase 1b EQUULEUS (MMY1001) trial, which evaluated daratumumab in combination with a variety of treatment regimens. Splitting the first infusion over 2 consecutive days reduced the duration of the infusion and resulted in a similar rate of infusion site reactions; concentrations were similar at the end of weekly dosing in patients who received the first infusion at once or over a 2-day period.

The adverse events reported in EQUULEUS (MMY1001) were largely similar to those seen in previous trials; the most common adverse events include infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, constipation, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy, and upper respiratory tract infection.

The approval providers “added flexibility for how patients may receive initial treatment,” Craig Tendler, MD, vice president of clinical development and global medical affairs at Janssen Research & Development, said in a statement.

[email protected]

The Food and Drug Administration has approved a split-dosing regimen for daratumumab (Darzalex) in patients with multiple myeloma, allowing the first infusion to be split over 2 days.

FDA approval is based on results from the global, multi-arm, phase 1b EQUULEUS (MMY1001) trial, which evaluated daratumumab in combination with a variety of treatment regimens. Splitting the first infusion over 2 consecutive days reduced the duration of the infusion and resulted in a similar rate of infusion site reactions; concentrations were similar at the end of weekly dosing in patients who received the first infusion at once or over a 2-day period.

The adverse events reported in EQUULEUS (MMY1001) were largely similar to those seen in previous trials; the most common adverse events include infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, constipation, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy, and upper respiratory tract infection.

The approval providers “added flexibility for how patients may receive initial treatment,” Craig Tendler, MD, vice president of clinical development and global medical affairs at Janssen Research & Development, said in a statement.

[email protected]

GRAND CAYMAN, CAYMAN ISLANDS – Atopic dermatitis (AD) researchers are serving up a lot more than oatmeal and steroids these days.

Moisturizers that confer skin barrier protection, lipid-replenishing topicals, and some biologics are available now or will soon be available for patients with AD, Joseph Fowler Jr., MD, said at the Caribbean Dermatology Symposium provided by Global Academy for Medical Education.

With the approval of dupilumab for moderate to severe disease in 2017, a biologic finally became available for treating AD, said Dr. Fowler of the University of Louisville (Ky.). While it’s not a cure and may take as long as 6 months to really kick in, “I think almost everyone gets some benefit from it. And although it’s not approved yet for anyone under 18, I’m sure it will be.”

He provided a brief rundown of dupilumab; crisaborole, another relatively new agent for AD; and some agents that are being investigated.

• Dupilumab. For AD, dupilumab, which inhibits interleukin-4 and interleukin-13 signaling, is usually started at 600 mg, then tapered to 300 mg subcutaneously every 2 weeks. Its pivotal data showed a mean 70% decrease in Eczema Area and Severity Index (EASI) scores over 16 weeks at that dose.*

“Again, I would say most patients do get benefit from this, but they might not see it for more than 3 months, and even up to 6 months. I’m not sure why, but some develop eye symptoms – I think these are more severe cases who also have respiratory atopy. I would also be interested to see if dupilumab might work on patients with chronic hand eczema,” he said.

• Crisaborole ointment 2%. A nonsteroidal topical phosphodiesterase 4 (PDE4) inhibitor approved in 2016 for mild to moderate AD in people aged 2 and older, crisaborole (Eucrisa) blocks the release of cyclic adenosine monophosphate (cAMP), which is elevated in AD. Lower cAMP levels lead to lower levels of inflammatory cytokines. In its pivotal phase 3 study, about 35% of patients achieved clinical success – an Investigator’s Static Global Assessment (ISGA) score of 0 or 1, or at least a two-grade improvement over baseline.

“In my opinion, it’s similar or slightly better than topical corticosteroids, and safer as well, especially in our younger patients, or when the face or intertriginous areas are involved,” Dr. Fowler said. “There is often some application site stinging and burning. If you put it in the fridge and get it good and cold when it goes on, that seems to moderate the sensation. It’s a good steroid-sparing option.”

Crisaborole is now being investigated for use in infants aged 3-24 months with mild to moderate AD.

• Tofacitinib ointment. This topical form of tofacitinib, an inhibitor of Janus kinase 1 and 3, is being evaluated in a placebo-controlled trial in adults with mild to moderate AD. There are also a few reports of oral tofacitinib improving AD, including a case report (Clin Exp Dermatol. 2017 Dec;42[8]:942-4). Dr. Fowler noted a small series of six adults with moderate to severe AD uncontrolled with methotrexate or azathioprine. The patients received oral tofacitinib 5 mg twice a day for 8-29 weeks; there was a mean 67% improvement in the Scoring Atopic Dermatitis (SCORAD) index.
• Ustekinumab. The interleukin-12 and -23 antagonist indicated for moderate to severe psoriasis has also made an appearance in the AD literature, including an Austrian report of three patients with severe AD who received 45 mg of ustekinumab (Stelara) subcutaneously at 0, 4 and 12 weeks. By week 16, all of them experienced a 50% reduction in their EASI score, with a marked reduction in interleukin-22 markers (J Am Acad Dermatol. 2017 Jan;76[1]:91-7.e3).

But no matter which therapy is chosen, regular moisturizing is critically important, Dr. Fowler remarked. Expensive prescription moisturizers are available, but he questioned whether they offer any cost-worthy extra benefit over a good nonprescription moisturizer.

“Do these super-moisturizers protect the skin barrier any more than petrolatum? I can’t answer that. They promise better results, but each patient and doc have to make the decision. If your patient can afford it, maybe some will be better for their skin, but really, it’s not as important as some of the other medications. So, I tell them, if cost is an issue, don’t worry about the fancy moisturizers.”

Dr. Fowler disclosed relationships with multiple pharmaceutical companies.

Global Academy and this news organization are owned by the same parent company.

Correction, 2/15/19: An earlier version of this article mischaracterized the chemical action of dupilumab.

[email protected]

GRAND CAYMAN, CAYMAN ISLANDS – Atopic dermatitis (AD) researchers are serving up a lot more than oatmeal and steroids these days.

Moisturizers that confer skin barrier protection, lipid-replenishing topicals, and some biologics are available now or will soon be available for patients with AD, Joseph Fowler Jr., MD, said at the Caribbean Dermatology Symposium provided by Global Academy for Medical Education.

With the approval of dupilumab for moderate to severe disease in 2017, a biologic finally became available for treating AD, said Dr. Fowler of the University of Louisville (Ky.). While it’s not a cure and may take as long as 6 months to really kick in, “I think almost everyone gets some benefit from it. And although it’s not approved yet for anyone under 18, I’m sure it will be.”

He provided a brief rundown of dupilumab; crisaborole, another relatively new agent for AD; and some agents that are being investigated.

• Dupilumab. For AD, dupilumab, which inhibits interleukin-4 and interleukin-13 signaling, is usually started at 600 mg, then tapered to 300 mg subcutaneously every 2 weeks. Its pivotal data showed a mean 70% decrease in Eczema Area and Severity Index (EASI) scores over 16 weeks at that dose.*

“Again, I would say most patients do get benefit from this, but they might not see it for more than 3 months, and even up to 6 months. I’m not sure why, but some develop eye symptoms – I think these are more severe cases who also have respiratory atopy. I would also be interested to see if dupilumab might work on patients with chronic hand eczema,” he said.

• Crisaborole ointment 2%. A nonsteroidal topical phosphodiesterase 4 (PDE4) inhibitor approved in 2016 for mild to moderate AD in people aged 2 and older, crisaborole (Eucrisa) blocks the release of cyclic adenosine monophosphate (cAMP), which is elevated in AD. Lower cAMP levels lead to lower levels of inflammatory cytokines. In its pivotal phase 3 study, about 35% of patients achieved clinical success – an Investigator’s Static Global Assessment (ISGA) score of 0 or 1, or at least a two-grade improvement over baseline.

“In my opinion, it’s similar or slightly better than topical corticosteroids, and safer as well, especially in our younger patients, or when the face or intertriginous areas are involved,” Dr. Fowler said. “There is often some application site stinging and burning. If you put it in the fridge and get it good and cold when it goes on, that seems to moderate the sensation. It’s a good steroid-sparing option.”

Crisaborole is now being investigated for use in infants aged 3-24 months with mild to moderate AD.

• Tofacitinib ointment. This topical form of tofacitinib, an inhibitor of Janus kinase 1 and 3, is being evaluated in a placebo-controlled trial in adults with mild to moderate AD. There are also a few reports of oral tofacitinib improving AD, including a case report (Clin Exp Dermatol. 2017 Dec;42[8]:942-4). Dr. Fowler noted a small series of six adults with moderate to severe AD uncontrolled with methotrexate or azathioprine. The patients received oral tofacitinib 5 mg twice a day for 8-29 weeks; there was a mean 67% improvement in the Scoring Atopic Dermatitis (SCORAD) index.
• Ustekinumab. The interleukin-12 and -23 antagonist indicated for moderate to severe psoriasis has also made an appearance in the AD literature, including an Austrian report of three patients with severe AD who received 45 mg of ustekinumab (Stelara) subcutaneously at 0, 4 and 12 weeks. By week 16, all of them experienced a 50% reduction in their EASI score, with a marked reduction in interleukin-22 markers (J Am Acad Dermatol. 2017 Jan;76[1]:91-7.e3).

But no matter which therapy is chosen, regular moisturizing is critically important, Dr. Fowler remarked. Expensive prescription moisturizers are available, but he questioned whether they offer any cost-worthy extra benefit over a good nonprescription moisturizer.

“Do these super-moisturizers protect the skin barrier any more than petrolatum? I can’t answer that. They promise better results, but each patient and doc have to make the decision. If your patient can afford it, maybe some will be better for their skin, but really, it’s not as important as some of the other medications. So, I tell them, if cost is an issue, don’t worry about the fancy moisturizers.”

Dr. Fowler disclosed relationships with multiple pharmaceutical companies.

Global Academy and this news organization are owned by the same parent company.

Correction, 2/15/19: An earlier version of this article mischaracterized the chemical action of dupilumab.

[email protected]

GRAND CAYMAN, CAYMAN ISLANDS – Atopic dermatitis (AD) researchers are serving up a lot more than oatmeal and steroids these days.

Moisturizers that confer skin barrier protection, lipid-replenishing topicals, and some biologics are available now or will soon be available for patients with AD, Joseph Fowler Jr., MD, said at the Caribbean Dermatology Symposium provided by Global Academy for Medical Education.

With the approval of dupilumab for moderate to severe disease in 2017, a biologic finally became available for treating AD, said Dr. Fowler of the University of Louisville (Ky.). While it’s not a cure and may take as long as 6 months to really kick in, “I think almost everyone gets some benefit from it. And although it’s not approved yet for anyone under 18, I’m sure it will be.”

He provided a brief rundown of dupilumab; crisaborole, another relatively new agent for AD; and some agents that are being investigated.

• Dupilumab. For AD, dupilumab, which inhibits interleukin-4 and interleukin-13 signaling, is usually started at 600 mg, then tapered to 300 mg subcutaneously every 2 weeks. Its pivotal data showed a mean 70% decrease in Eczema Area and Severity Index (EASI) scores over 16 weeks at that dose.*

“Again, I would say most patients do get benefit from this, but they might not see it for more than 3 months, and even up to 6 months. I’m not sure why, but some develop eye symptoms – I think these are more severe cases who also have respiratory atopy. I would also be interested to see if dupilumab might work on patients with chronic hand eczema,” he said.

• Crisaborole ointment 2%. A nonsteroidal topical phosphodiesterase 4 (PDE4) inhibitor approved in 2016 for mild to moderate AD in people aged 2 and older, crisaborole (Eucrisa) blocks the release of cyclic adenosine monophosphate (cAMP), which is elevated in AD. Lower cAMP levels lead to lower levels of inflammatory cytokines. In its pivotal phase 3 study, about 35% of patients achieved clinical success – an Investigator’s Static Global Assessment (ISGA) score of 0 or 1, or at least a two-grade improvement over baseline.

“In my opinion, it’s similar or slightly better than topical corticosteroids, and safer as well, especially in our younger patients, or when the face or intertriginous areas are involved,” Dr. Fowler said. “There is often some application site stinging and burning. If you put it in the fridge and get it good and cold when it goes on, that seems to moderate the sensation. It’s a good steroid-sparing option.”

Crisaborole is now being investigated for use in infants aged 3-24 months with mild to moderate AD.

• Tofacitinib ointment. This topical form of tofacitinib, an inhibitor of Janus kinase 1 and 3, is being evaluated in a placebo-controlled trial in adults with mild to moderate AD. There are also a few reports of oral tofacitinib improving AD, including a case report (Clin Exp Dermatol. 2017 Dec;42[8]:942-4). Dr. Fowler noted a small series of six adults with moderate to severe AD uncontrolled with methotrexate or azathioprine. The patients received oral tofacitinib 5 mg twice a day for 8-29 weeks; there was a mean 67% improvement in the Scoring Atopic Dermatitis (SCORAD) index.
• Ustekinumab. The interleukin-12 and -23 antagonist indicated for moderate to severe psoriasis has also made an appearance in the AD literature, including an Austrian report of three patients with severe AD who received 45 mg of ustekinumab (Stelara) subcutaneously at 0, 4 and 12 weeks. By week 16, all of them experienced a 50% reduction in their EASI score, with a marked reduction in interleukin-22 markers (J Am Acad Dermatol. 2017 Jan;76[1]:91-7.e3).

But no matter which therapy is chosen, regular moisturizing is critically important, Dr. Fowler remarked. Expensive prescription moisturizers are available, but he questioned whether they offer any cost-worthy extra benefit over a good nonprescription moisturizer.

“Do these super-moisturizers protect the skin barrier any more than petrolatum? I can’t answer that. They promise better results, but each patient and doc have to make the decision. If your patient can afford it, maybe some will be better for their skin, but really, it’s not as important as some of the other medications. So, I tell them, if cost is an issue, don’t worry about the fancy moisturizers.”

Dr. Fowler disclosed relationships with multiple pharmaceutical companies.

Global Academy and this news organization are owned by the same parent company.

Correction, 2/15/19: An earlier version of this article mischaracterized the chemical action of dupilumab.

[email protected]

SAN FRANCISCO – When given the same hormonal therapy for chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), African American men live about 4 months longer than do white men, finds a retrospective cohort study being reported at the 2019 Genitourinary Cancers Symposium.

“We know that African American men have a higher risk of mCRPC and worse survival than white men,” said lead study author Megan McNamara, MD, of Duke University, Durham, N.C. “However, despite this, there is also evidence to suggest that African Americans with advanced prostate cancer actually have better outcomes in response to several prostate cancer treatments compared to Caucasians.”

She and her colleagues analyzed data from the Veterans Health Administration database for a 5-year period (2013-2018), focusing on 2,123 white and 787 African American male veterans with chemotherapy-naive mCRPC who were treated with the anti-androgen abiraterone (Zytiga) or the androgen receptor inhibitor enzalutamide (Xtandi). Overall survival was measured from the first prescription claim for either drug following medical or surgical castration.

Main results reported in a presscast leading up to the symposium showed that with a median follow-up of about 1.6 years, median overall survival was 30 months for African American men, compared with 26 months for white men. The difference corresponded to a significantly lower risk of death for African American men in both univariate analysis (hazard ratio, 0.887; P = .0435) and multivariate analysis adjusted for age and comorbidities (HR, 0.826; P = .0020).

“When controlling for access to care through a single-payer system – in this case, the VA Health System – in chemotherapy-naive mCRPC patients, African Americans may have better overall survival than Caucasians when treated with abiraterone or enzalutamide,” Dr. McNamara summarized. “These results are consistent with what we have seen in prior studies in this population involving docetaxel (Taxotere), sipuleucel-T (Provenge), and abiraterone.”

Importantly, the data expand on previous findings for abiraterone in the Abi Race study, she noted. That study established that African American men had a better prostate-specific antigen (PSA) response to the drug (J Clin Oncol. 2018 Jun 7. doi: 10.1200/JCO.2018.36.18_suppl.LBA5009).

The new findings do not alter but rather reinforce current clinical practice, according to Dr. McNamara. “These are standard-of-care treatments, and it’s important that we have real-world studies that show that the standard-of-care treatments really work,” she elaborated. “So I don’t think that they necessarily change what we are doing. But they reinforce what we are already doing, and that it’s important that we make sure that every African American who is eligible for these medicines gets them.

“Our study is retrospective,” she acknowledged. “But it emphasizes the need for prospective trials in order to validate these findings and in order to try to understand the mechanism that underlies these differences in survival outcomes between African Americans and Caucasians with mCRPC when treated with these novel hormone therapies.”

The data are “very provocative, and it adds to an emerging database that if confirmed prospectively, really changes the way we think about racial differences,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.

Full results of the study will be reported at the symposium, which is sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. McNamara disclosed that she receives travel, accommodations, and/or expenses from Clovis Oncology; honoraria from Bayer and Exelixis; and research funding (institutional) from Bayer, Seattle Genetics/Astellas, Agensys, Clovis Oncology, and Janssen. The study was funded by Pfizer.
 

SOURCE: McNamara MA et al. Abstract 212.

SAN FRANCISCO – When given the same hormonal therapy for chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), African American men live about 4 months longer than do white men, finds a retrospective cohort study being reported at the 2019 Genitourinary Cancers Symposium.

“We know that African American men have a higher risk of mCRPC and worse survival than white men,” said lead study author Megan McNamara, MD, of Duke University, Durham, N.C. “However, despite this, there is also evidence to suggest that African Americans with advanced prostate cancer actually have better outcomes in response to several prostate cancer treatments compared to Caucasians.”

She and her colleagues analyzed data from the Veterans Health Administration database for a 5-year period (2013-2018), focusing on 2,123 white and 787 African American male veterans with chemotherapy-naive mCRPC who were treated with the anti-androgen abiraterone (Zytiga) or the androgen receptor inhibitor enzalutamide (Xtandi). Overall survival was measured from the first prescription claim for either drug following medical or surgical castration.

Main results reported in a presscast leading up to the symposium showed that with a median follow-up of about 1.6 years, median overall survival was 30 months for African American men, compared with 26 months for white men. The difference corresponded to a significantly lower risk of death for African American men in both univariate analysis (hazard ratio, 0.887; P = .0435) and multivariate analysis adjusted for age and comorbidities (HR, 0.826; P = .0020).

“When controlling for access to care through a single-payer system – in this case, the VA Health System – in chemotherapy-naive mCRPC patients, African Americans may have better overall survival than Caucasians when treated with abiraterone or enzalutamide,” Dr. McNamara summarized. “These results are consistent with what we have seen in prior studies in this population involving docetaxel (Taxotere), sipuleucel-T (Provenge), and abiraterone.”

Importantly, the data expand on previous findings for abiraterone in the Abi Race study, she noted. That study established that African American men had a better prostate-specific antigen (PSA) response to the drug (J Clin Oncol. 2018 Jun 7. doi: 10.1200/JCO.2018.36.18_suppl.LBA5009).

The new findings do not alter but rather reinforce current clinical practice, according to Dr. McNamara. “These are standard-of-care treatments, and it’s important that we have real-world studies that show that the standard-of-care treatments really work,” she elaborated. “So I don’t think that they necessarily change what we are doing. But they reinforce what we are already doing, and that it’s important that we make sure that every African American who is eligible for these medicines gets them.

“Our study is retrospective,” she acknowledged. “But it emphasizes the need for prospective trials in order to validate these findings and in order to try to understand the mechanism that underlies these differences in survival outcomes between African Americans and Caucasians with mCRPC when treated with these novel hormone therapies.”

The data are “very provocative, and it adds to an emerging database that if confirmed prospectively, really changes the way we think about racial differences,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.

Full results of the study will be reported at the symposium, which is sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. McNamara disclosed that she receives travel, accommodations, and/or expenses from Clovis Oncology; honoraria from Bayer and Exelixis; and research funding (institutional) from Bayer, Seattle Genetics/Astellas, Agensys, Clovis Oncology, and Janssen. The study was funded by Pfizer.
 

SOURCE: McNamara MA et al. Abstract 212.

SAN FRANCISCO – When given the same hormonal therapy for chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), African American men live about 4 months longer than do white men, finds a retrospective cohort study being reported at the 2019 Genitourinary Cancers Symposium.

“We know that African American men have a higher risk of mCRPC and worse survival than white men,” said lead study author Megan McNamara, MD, of Duke University, Durham, N.C. “However, despite this, there is also evidence to suggest that African Americans with advanced prostate cancer actually have better outcomes in response to several prostate cancer treatments compared to Caucasians.”

She and her colleagues analyzed data from the Veterans Health Administration database for a 5-year period (2013-2018), focusing on 2,123 white and 787 African American male veterans with chemotherapy-naive mCRPC who were treated with the anti-androgen abiraterone (Zytiga) or the androgen receptor inhibitor enzalutamide (Xtandi). Overall survival was measured from the first prescription claim for either drug following medical or surgical castration.

Main results reported in a presscast leading up to the symposium showed that with a median follow-up of about 1.6 years, median overall survival was 30 months for African American men, compared with 26 months for white men. The difference corresponded to a significantly lower risk of death for African American men in both univariate analysis (hazard ratio, 0.887; P = .0435) and multivariate analysis adjusted for age and comorbidities (HR, 0.826; P = .0020).

“When controlling for access to care through a single-payer system – in this case, the VA Health System – in chemotherapy-naive mCRPC patients, African Americans may have better overall survival than Caucasians when treated with abiraterone or enzalutamide,” Dr. McNamara summarized. “These results are consistent with what we have seen in prior studies in this population involving docetaxel (Taxotere), sipuleucel-T (Provenge), and abiraterone.”

Importantly, the data expand on previous findings for abiraterone in the Abi Race study, she noted. That study established that African American men had a better prostate-specific antigen (PSA) response to the drug (J Clin Oncol. 2018 Jun 7. doi: 10.1200/JCO.2018.36.18_suppl.LBA5009).

The new findings do not alter but rather reinforce current clinical practice, according to Dr. McNamara. “These are standard-of-care treatments, and it’s important that we have real-world studies that show that the standard-of-care treatments really work,” she elaborated. “So I don’t think that they necessarily change what we are doing. But they reinforce what we are already doing, and that it’s important that we make sure that every African American who is eligible for these medicines gets them.

“Our study is retrospective,” she acknowledged. “But it emphasizes the need for prospective trials in order to validate these findings and in order to try to understand the mechanism that underlies these differences in survival outcomes between African Americans and Caucasians with mCRPC when treated with these novel hormone therapies.”

The data are “very provocative, and it adds to an emerging database that if confirmed prospectively, really changes the way we think about racial differences,” said ASCO expert and presscast moderator Robert Dreicer, MD, MS, MACP, FASCO, deputy director and associate director of clinical research at the University of Virginia Cancer Center and professor of medicine and urology at the University of Virginia, Charlottesville.

Full results of the study will be reported at the symposium, which is sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. McNamara disclosed that she receives travel, accommodations, and/or expenses from Clovis Oncology; honoraria from Bayer and Exelixis; and research funding (institutional) from Bayer, Seattle Genetics/Astellas, Agensys, Clovis Oncology, and Janssen. The study was funded by Pfizer.
 

SOURCE: McNamara MA et al. Abstract 212.

In this episode, Igor Galynker, MD, stops by to talk about suicide with Lorenzo Norris, MD. One major topic of conversation centers around suicide-specific diagnosis. And later, Renee Kohanski, MD, talks about the importance of communication. You can listen to Dr. Galynker’s first appearance on the Psychcast here.

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Apple Podcasts
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Spotify


 

In this episode, Igor Galynker, MD, stops by to talk about suicide with Lorenzo Norris, MD. One major topic of conversation centers around suicide-specific diagnosis. And later, Renee Kohanski, MD, talks about the importance of communication. You can listen to Dr. Galynker’s first appearance on the Psychcast here.

Amazon
Apple Podcasts
Google Podcasts
Spotify


 

In this episode, Igor Galynker, MD, stops by to talk about suicide with Lorenzo Norris, MD. One major topic of conversation centers around suicide-specific diagnosis. And later, Renee Kohanski, MD, talks about the importance of communication. You can listen to Dr. Galynker’s first appearance on the Psychcast here.

Amazon
Apple Podcasts
Google Podcasts
Spotify


 

New research has revealed considerable disparity between rheumatologists’ clinical diagnosis of fibromyalgia and fibromyalgia criteria-based diagnosis, particularly the most recent revision of criteria from 2011 that rely on patients’ self-report of symptoms.

Frederick Wolfe, MD, of the National Data Bank for Rheumatic Diseases and the University of Kansas, Wichita, and his colleagues reported in Arthritis Care & Research that clinicians failed to identify almost half of cases that met the 2011 modification of the American College of Rheumatology’s self-report criteria for fibromyalgia during a 3-month period at Rush Medical College, Chicago. This led them to conclude that the “overall agreement between clinicians’ diagnosis of fibromyalgia and diagnosis by fibromyalgia criteria is only fair.”

The findings call into question studies of fibromyalgia based on ICD-10 diagnosis, according to the authors.

Several widely accepted criteria sets have provided definitions and methods of diagnosis, but a number of studies have suggested that fibromyalgia is overdiagnosed, the authors wrote.

“In the current study, we consider underdiagnosis as well as the form of overdiagnosis that lead to diagnosis when fibromyalgia criteria are not satisfied and symptoms are insufficient for diagnosis,” they added.

The research included 497 consecutive patients attending the Rush Medical College rheumatology clinic who completed a questionnaire assessing fibromyalgia diagnostic variables used in the ACR 2010 preliminary diagnostic criteria for fibromyalgia and its 2011 modification for self-report immediately prior to being seen at the clinic. Clinicians were not given instructions on how any diseases were to be diagnosed, including no instructions on using 2011 fibromyalgia criteria.


The results showed that 121 (24.3%) of the patients satisfied the 2011 fibromyalgia criteria. The agreement between clinicians and criteria was 79.2%, but agreement beyond chance was considered “fair” based on a kappa score of 0.41 and a probabilistic benchmark interval of 0.21-0.40. The researchers wrote that this benchmark represents “the probability for each coefficient of falling into the selected benchmark interval along with the cumulative probability of exceeding the predetermined threshold associated with the interval.”

A total of 104 (20.9%) received a clinician ICD-10 diagnosis of fibromyalgia, but only 61 (58.7%) actually satisfied criteria. Physicians failed to identify 60 (49.6%) criteria-positive patients and incorrectly identified 43 (11.4%) criteria-negative patients.

In a subset of 88 patients with RA, agreement was 84.1%, and the kappa score was 0.32, indicating “slight to fair” agreement (probabilistic benchmark interval, 0.00-0.20). Among 13 RA patients with criteria-positive fibromyalgia, 5 were identified by clinicians; among those who were criteria negative, 6 were deemed positive by clinicians.

The authors noted than “even worse” results were obtained in patients with systemic lupus erythematosus, where the agreement between criteria and clinician ICD diagnosis yielded a kappa value of 0.08. In patients with osteoarthritis, the kappa score was 0.51 (probabilistic benchmark interval, 0.21-0.40).

Overall, the results showed that women and patients with more symptoms but fewer pain areas were more likely to receive a clinician’s diagnosis than to satisfy fibromyalgia criteria. “Clinicians gave greater weight in making a diagnosis to being a woman and having increased symptoms and were willing to diagnose patients with lower WPI [Widespread Pain Index] and PSD [polysymptomatic distress] scores,” the researchers noted.

Dr. Wolfe and his associates wrote that it is unclear why the physicians in the study who misclassified fibromyalgia and missed patients with the diagnosis did not do better. “They may have simply misdiagnosed the condition or not accepted the use of the formal diagnostic system as necessary or clinically useful for identifying fibromyalgia in routine care.”

The researchers noted that it is likely that diagnosis in the community by general physicians, for whom the criteria are not as well known, is even more inaccurate. “It is likely that misdiagnosis is a public health problem and one that can lead to overdiagnosis and overtreatment as well as to inappropriate treatment of individuals not recognized to have fibromyalgia symptoms.”

No disclosures or funding were reported.

SOURCE: Wolfe F et al. Arthritis Care Res. 2019 Feb 6. doi: 10.1002/acr.23731.

New research has revealed considerable disparity between rheumatologists’ clinical diagnosis of fibromyalgia and fibromyalgia criteria-based diagnosis, particularly the most recent revision of criteria from 2011 that rely on patients’ self-report of symptoms.

Frederick Wolfe, MD, of the National Data Bank for Rheumatic Diseases and the University of Kansas, Wichita, and his colleagues reported in Arthritis Care & Research that clinicians failed to identify almost half of cases that met the 2011 modification of the American College of Rheumatology’s self-report criteria for fibromyalgia during a 3-month period at Rush Medical College, Chicago. This led them to conclude that the “overall agreement between clinicians’ diagnosis of fibromyalgia and diagnosis by fibromyalgia criteria is only fair.”

The findings call into question studies of fibromyalgia based on ICD-10 diagnosis, according to the authors.

Several widely accepted criteria sets have provided definitions and methods of diagnosis, but a number of studies have suggested that fibromyalgia is overdiagnosed, the authors wrote.

“In the current study, we consider underdiagnosis as well as the form of overdiagnosis that lead to diagnosis when fibromyalgia criteria are not satisfied and symptoms are insufficient for diagnosis,” they added.

The research included 497 consecutive patients attending the Rush Medical College rheumatology clinic who completed a questionnaire assessing fibromyalgia diagnostic variables used in the ACR 2010 preliminary diagnostic criteria for fibromyalgia and its 2011 modification for self-report immediately prior to being seen at the clinic. Clinicians were not given instructions on how any diseases were to be diagnosed, including no instructions on using 2011 fibromyalgia criteria.


The results showed that 121 (24.3%) of the patients satisfied the 2011 fibromyalgia criteria. The agreement between clinicians and criteria was 79.2%, but agreement beyond chance was considered “fair” based on a kappa score of 0.41 and a probabilistic benchmark interval of 0.21-0.40. The researchers wrote that this benchmark represents “the probability for each coefficient of falling into the selected benchmark interval along with the cumulative probability of exceeding the predetermined threshold associated with the interval.”

A total of 104 (20.9%) received a clinician ICD-10 diagnosis of fibromyalgia, but only 61 (58.7%) actually satisfied criteria. Physicians failed to identify 60 (49.6%) criteria-positive patients and incorrectly identified 43 (11.4%) criteria-negative patients.

In a subset of 88 patients with RA, agreement was 84.1%, and the kappa score was 0.32, indicating “slight to fair” agreement (probabilistic benchmark interval, 0.00-0.20). Among 13 RA patients with criteria-positive fibromyalgia, 5 were identified by clinicians; among those who were criteria negative, 6 were deemed positive by clinicians.

The authors noted than “even worse” results were obtained in patients with systemic lupus erythematosus, where the agreement between criteria and clinician ICD diagnosis yielded a kappa value of 0.08. In patients with osteoarthritis, the kappa score was 0.51 (probabilistic benchmark interval, 0.21-0.40).

Overall, the results showed that women and patients with more symptoms but fewer pain areas were more likely to receive a clinician’s diagnosis than to satisfy fibromyalgia criteria. “Clinicians gave greater weight in making a diagnosis to being a woman and having increased symptoms and were willing to diagnose patients with lower WPI [Widespread Pain Index] and PSD [polysymptomatic distress] scores,” the researchers noted.

Dr. Wolfe and his associates wrote that it is unclear why the physicians in the study who misclassified fibromyalgia and missed patients with the diagnosis did not do better. “They may have simply misdiagnosed the condition or not accepted the use of the formal diagnostic system as necessary or clinically useful for identifying fibromyalgia in routine care.”

The researchers noted that it is likely that diagnosis in the community by general physicians, for whom the criteria are not as well known, is even more inaccurate. “It is likely that misdiagnosis is a public health problem and one that can lead to overdiagnosis and overtreatment as well as to inappropriate treatment of individuals not recognized to have fibromyalgia symptoms.”

No disclosures or funding were reported.

SOURCE: Wolfe F et al. Arthritis Care Res. 2019 Feb 6. doi: 10.1002/acr.23731.

New research has revealed considerable disparity between rheumatologists’ clinical diagnosis of fibromyalgia and fibromyalgia criteria-based diagnosis, particularly the most recent revision of criteria from 2011 that rely on patients’ self-report of symptoms.

Frederick Wolfe, MD, of the National Data Bank for Rheumatic Diseases and the University of Kansas, Wichita, and his colleagues reported in Arthritis Care & Research that clinicians failed to identify almost half of cases that met the 2011 modification of the American College of Rheumatology’s self-report criteria for fibromyalgia during a 3-month period at Rush Medical College, Chicago. This led them to conclude that the “overall agreement between clinicians’ diagnosis of fibromyalgia and diagnosis by fibromyalgia criteria is only fair.”

The findings call into question studies of fibromyalgia based on ICD-10 diagnosis, according to the authors.

Several widely accepted criteria sets have provided definitions and methods of diagnosis, but a number of studies have suggested that fibromyalgia is overdiagnosed, the authors wrote.

“In the current study, we consider underdiagnosis as well as the form of overdiagnosis that lead to diagnosis when fibromyalgia criteria are not satisfied and symptoms are insufficient for diagnosis,” they added.

The research included 497 consecutive patients attending the Rush Medical College rheumatology clinic who completed a questionnaire assessing fibromyalgia diagnostic variables used in the ACR 2010 preliminary diagnostic criteria for fibromyalgia and its 2011 modification for self-report immediately prior to being seen at the clinic. Clinicians were not given instructions on how any diseases were to be diagnosed, including no instructions on using 2011 fibromyalgia criteria.


The results showed that 121 (24.3%) of the patients satisfied the 2011 fibromyalgia criteria. The agreement between clinicians and criteria was 79.2%, but agreement beyond chance was considered “fair” based on a kappa score of 0.41 and a probabilistic benchmark interval of 0.21-0.40. The researchers wrote that this benchmark represents “the probability for each coefficient of falling into the selected benchmark interval along with the cumulative probability of exceeding the predetermined threshold associated with the interval.”

A total of 104 (20.9%) received a clinician ICD-10 diagnosis of fibromyalgia, but only 61 (58.7%) actually satisfied criteria. Physicians failed to identify 60 (49.6%) criteria-positive patients and incorrectly identified 43 (11.4%) criteria-negative patients.

In a subset of 88 patients with RA, agreement was 84.1%, and the kappa score was 0.32, indicating “slight to fair” agreement (probabilistic benchmark interval, 0.00-0.20). Among 13 RA patients with criteria-positive fibromyalgia, 5 were identified by clinicians; among those who were criteria negative, 6 were deemed positive by clinicians.

The authors noted than “even worse” results were obtained in patients with systemic lupus erythematosus, where the agreement between criteria and clinician ICD diagnosis yielded a kappa value of 0.08. In patients with osteoarthritis, the kappa score was 0.51 (probabilistic benchmark interval, 0.21-0.40).

Overall, the results showed that women and patients with more symptoms but fewer pain areas were more likely to receive a clinician’s diagnosis than to satisfy fibromyalgia criteria. “Clinicians gave greater weight in making a diagnosis to being a woman and having increased symptoms and were willing to diagnose patients with lower WPI [Widespread Pain Index] and PSD [polysymptomatic distress] scores,” the researchers noted.

Dr. Wolfe and his associates wrote that it is unclear why the physicians in the study who misclassified fibromyalgia and missed patients with the diagnosis did not do better. “They may have simply misdiagnosed the condition or not accepted the use of the formal diagnostic system as necessary or clinically useful for identifying fibromyalgia in routine care.”

The researchers noted that it is likely that diagnosis in the community by general physicians, for whom the criteria are not as well known, is even more inaccurate. “It is likely that misdiagnosis is a public health problem and one that can lead to overdiagnosis and overtreatment as well as to inappropriate treatment of individuals not recognized to have fibromyalgia symptoms.”

No disclosures or funding were reported.

SOURCE: Wolfe F et al. Arthritis Care Res. 2019 Feb 6. doi: 10.1002/acr.23731.

Although PTSD is strongly linked to cardiovascular disease, it is not an independent risk factor, results of a recent analysis suggest.

Brett Mulcahy/ThinkStock

Instead, the association between PTSD and cardiovascular disease (CVD) is likely explained by factors such as smoking and physical and psychiatric disorders, according to authors of the analysis based on EHR data for more than 4,000 U.S. veterans.

Individuals with PTSD were 41% more likely than those without it to develop cardiovascular disease, according to the researchers, led by Jeffrey F. Scherrer, PhD, of Saint Louis University and the Harry S. Truman Veterans Administration Medical Center in Columbia, Mo.

However, PTSD was not associated with CVD in the study after adjustment for physical, psychiatric, and behavioral conditions, Dr. Scherrer and his colleagues reported in the Journal of the American Heart Association.

“Recognizing that PTSD does not preordain CVD may empower patients to seek care to prevent and/or manage CVD risk factors,” they wrote.

Health behavior change and management of chronic disease can mitigate risk of CVD in patients with or without PTSD, they added.

This result contrasts with earlier work associating PTSD with CVD, the authors wrote. In particular, a few well-designed studies did indicate that the link between PTSD and CVD was weakened, but still significant, when controlling for traditional CVD risk factors such as smoking, diabetes, and hypertension.

In the current study, investigators controlled for a variety of physical and psychiatric conditions, as well as smoking, in data for Veterans Affairs patients, of whom 2,519 had a PTSD diagnosis and 1,659 did not. These patients were 87% male, 60% white, and had an average age of 50 years.

The investigators found that PTSD was significantly associated with incident CVD after adjusting for age, with a hazard ratio of 1.41 (95% confidence interval, 1.21-1.63; P less than .0001).

That association remained significant after adjusting for diabetes, obesity, hypertension, and hyperlipidemia, but the magnitude of the association dropped considerably (HR, 1.23; 95% CI, 1.06-1.44; P less than .007) and dropped out altogether after controlling for smoking, substance abuse, sleep disorders, anxiety, and depression (HR, 0.96; 95% CI, 0.81-1.15; P = .691).

Taken together, these findings suggest the association with incident CVD may be explained by combinations of comorbidities that are more prevalent in patients who have PTSD than in those who do not, Dr. Scherrer and his coauthors wrote.

“Because these conditions are more common in patients with PTSD, closer monitoring for comorbidities may be warranted,” they concluded. “Early detection and effective management may reduce the burden of CVD associated with PTSD.”

One study coinvestigator reported consulting for Noblis Therapeutics and grant-related disclosures with the Department of Veterans Affairs, Department of Defense, and National Institute of Mental Health.

SOURCE: Scherrer JF et al. J Am Heart Assoc. 2019 Feb 13. doi: 10.1161/JAHA.118.011133.

Although PTSD is strongly linked to cardiovascular disease, it is not an independent risk factor, results of a recent analysis suggest.

Brett Mulcahy/ThinkStock

Instead, the association between PTSD and cardiovascular disease (CVD) is likely explained by factors such as smoking and physical and psychiatric disorders, according to authors of the analysis based on EHR data for more than 4,000 U.S. veterans.

Individuals with PTSD were 41% more likely than those without it to develop cardiovascular disease, according to the researchers, led by Jeffrey F. Scherrer, PhD, of Saint Louis University and the Harry S. Truman Veterans Administration Medical Center in Columbia, Mo.

However, PTSD was not associated with CVD in the study after adjustment for physical, psychiatric, and behavioral conditions, Dr. Scherrer and his colleagues reported in the Journal of the American Heart Association.

“Recognizing that PTSD does not preordain CVD may empower patients to seek care to prevent and/or manage CVD risk factors,” they wrote.

Health behavior change and management of chronic disease can mitigate risk of CVD in patients with or without PTSD, they added.

This result contrasts with earlier work associating PTSD with CVD, the authors wrote. In particular, a few well-designed studies did indicate that the link between PTSD and CVD was weakened, but still significant, when controlling for traditional CVD risk factors such as smoking, diabetes, and hypertension.

In the current study, investigators controlled for a variety of physical and psychiatric conditions, as well as smoking, in data for Veterans Affairs patients, of whom 2,519 had a PTSD diagnosis and 1,659 did not. These patients were 87% male, 60% white, and had an average age of 50 years.

The investigators found that PTSD was significantly associated with incident CVD after adjusting for age, with a hazard ratio of 1.41 (95% confidence interval, 1.21-1.63; P less than .0001).

That association remained significant after adjusting for diabetes, obesity, hypertension, and hyperlipidemia, but the magnitude of the association dropped considerably (HR, 1.23; 95% CI, 1.06-1.44; P less than .007) and dropped out altogether after controlling for smoking, substance abuse, sleep disorders, anxiety, and depression (HR, 0.96; 95% CI, 0.81-1.15; P = .691).

Taken together, these findings suggest the association with incident CVD may be explained by combinations of comorbidities that are more prevalent in patients who have PTSD than in those who do not, Dr. Scherrer and his coauthors wrote.

“Because these conditions are more common in patients with PTSD, closer monitoring for comorbidities may be warranted,” they concluded. “Early detection and effective management may reduce the burden of CVD associated with PTSD.”

One study coinvestigator reported consulting for Noblis Therapeutics and grant-related disclosures with the Department of Veterans Affairs, Department of Defense, and National Institute of Mental Health.

SOURCE: Scherrer JF et al. J Am Heart Assoc. 2019 Feb 13. doi: 10.1161/JAHA.118.011133.

Although PTSD is strongly linked to cardiovascular disease, it is not an independent risk factor, results of a recent analysis suggest.

Brett Mulcahy/ThinkStock

Instead, the association between PTSD and cardiovascular disease (CVD) is likely explained by factors such as smoking and physical and psychiatric disorders, according to authors of the analysis based on EHR data for more than 4,000 U.S. veterans.

Individuals with PTSD were 41% more likely than those without it to develop cardiovascular disease, according to the researchers, led by Jeffrey F. Scherrer, PhD, of Saint Louis University and the Harry S. Truman Veterans Administration Medical Center in Columbia, Mo.

However, PTSD was not associated with CVD in the study after adjustment for physical, psychiatric, and behavioral conditions, Dr. Scherrer and his colleagues reported in the Journal of the American Heart Association.

“Recognizing that PTSD does not preordain CVD may empower patients to seek care to prevent and/or manage CVD risk factors,” they wrote.

Health behavior change and management of chronic disease can mitigate risk of CVD in patients with or without PTSD, they added.

This result contrasts with earlier work associating PTSD with CVD, the authors wrote. In particular, a few well-designed studies did indicate that the link between PTSD and CVD was weakened, but still significant, when controlling for traditional CVD risk factors such as smoking, diabetes, and hypertension.

In the current study, investigators controlled for a variety of physical and psychiatric conditions, as well as smoking, in data for Veterans Affairs patients, of whom 2,519 had a PTSD diagnosis and 1,659 did not. These patients were 87% male, 60% white, and had an average age of 50 years.

The investigators found that PTSD was significantly associated with incident CVD after adjusting for age, with a hazard ratio of 1.41 (95% confidence interval, 1.21-1.63; P less than .0001).

That association remained significant after adjusting for diabetes, obesity, hypertension, and hyperlipidemia, but the magnitude of the association dropped considerably (HR, 1.23; 95% CI, 1.06-1.44; P less than .007) and dropped out altogether after controlling for smoking, substance abuse, sleep disorders, anxiety, and depression (HR, 0.96; 95% CI, 0.81-1.15; P = .691).

Taken together, these findings suggest the association with incident CVD may be explained by combinations of comorbidities that are more prevalent in patients who have PTSD than in those who do not, Dr. Scherrer and his coauthors wrote.

“Because these conditions are more common in patients with PTSD, closer monitoring for comorbidities may be warranted,” they concluded. “Early detection and effective management may reduce the burden of CVD associated with PTSD.”

One study coinvestigator reported consulting for Noblis Therapeutics and grant-related disclosures with the Department of Veterans Affairs, Department of Defense, and National Institute of Mental Health.

SOURCE: Scherrer JF et al. J Am Heart Assoc. 2019 Feb 13. doi: 10.1161/JAHA.118.011133.