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Gender-affirming care: The role of the pediatrician in a changing landscape
As the political targeting of transgender youth and families continues to play out on the national stage, it is more important than ever for pediatricians and other primary care providers to support this vulnerable population by defending the recommendations and guidelines of reputable medical organizations based in science and to show grace and humility in caring for their patients.
Guidelines and resources
All leading medical groups in the United States with statements or policies related to gender-affirming care (including the American Medical Association, the American Academy of Pediatrics, the Society for Adolescent Health and Medicine, the Pediatric Endocrine Society, the American Academy of Child and Adolescent Psychiatry, and many more) recognize that this care is medically necessary and that exclusions for gender-related services are harmful to patients and their families. As pediatricians, families and youth rely on our expertise and guidance related to childhood and adolescent development, including the development of gender identity and ways to create safe and supportive environments needed for youth to reach their full potential.1
While pediatricians are experts in youth development, some may have had limited access to training specific to LGBTQ+ identity development and interventions related to gender-affirming care. There are, however, readily accessible resources to help guide pediatricians in providing support and recommendations to families with concerns around gender or sexuality (See Resources). The American Academy of Pediatrics and Bright Futures recommend discussing the differences between assigned sex at birth and gender identity development with parents of those younger than 12 months of age as well as beginning to discuss and explore gender identity with all youth beginning at 4-5 years of age. Beginning at 8 years of age, pediatricians are also recommended to assess for a patient’s understanding and feelings toward emerging puberty to identify any potential concerns for gender dysphoria.2 If concerns or questions emerge from screening, the family can then be referred to a gender-affirming care specialist for more support.
Gender dysphoria and gender-affirming care
Gender dysphoria may present in different ways and at different times for each patient. Some patients may present early in childhood with gender-diverse behaviors or the assertion of a gender identity different than their assigned sex at birth. However, the most commonly seen presentation is just prior to or during puberty, when one’s physical body starts to change in ways that are not consistent with their gender identity. Many patients report distress around gender before this time, but the distress that comes with the physical changes of puberty often prompts patients to reach out to parents, friends, and/or medical providers for help. Other than youth specifically disclosing their gender identity, as with any life stressors, gender dysphoria may initially present with a decline in school or social functioning, increased mood irritability, depression, or anxiety.3
The goal of support prior to puberty is for youth to grow and thrive as any other child and to not have gender dysphoria get in the way of normal development and social functioning.4 Some families will pursue social transition, the process of making changes within different areas of social interaction (such as name, pronouns, clothing, hairstyle, etc.) to decrease distress around gender. The decision of whether to pursue social transition is unique to each patient and family. The goal of this process is to allow youth to explore these changes in an effort to decrease the distress they experience in social interactions. Youth should be centered in this process and be the leader of any potential changes with parents and schools providing safe and supportive environments.5 Social transition has been shown to decrease rates of depression in gender-diverse youth to the same level as that of their cisgender peers.6
It is important to note that there are no recommended medical interventions for gender-affirming care before the time of puberty and, once a patient reaches Sexual Maturity Rating II (early puberty), the first potential treatment option is the reversible suppression of puberty using gonadotropin-releasing hormone (GnRH) analogues. The goal of this type of medication is to allow youth more time to explore their gender and avoid the permanent physical changes that occur during their endogenous puberty that can have a significant negative impact on their gender dysphoria and psychosocial functioning. Youth and their families can then later decide to discontinue the medication and go through their endogenous puberty or to proceed with gender-affirming hormone treatment.7
With the growing number of states who have or are attempting to ban gender-affirming care for youth, more patients and families will be left with no options for accessing this potentially life-saving care and support within their home state. Some families have already been forced to relocate to more supportive environments or to travel significant distances to receive medically necessary care.8 This summer, the American Academy of Pediatrics reaffirmed their current policy stating, “The AAP opposes any laws or regulations that discriminate against transgender and gender-diverse individuals, or that interfere in the doctor-patient relationship,” and they “support giving transgender adolescents access to the health care they need.”9
Pediatricians should continue to utilize existing resources for recommended routine screening and subsequent referral for patients or families with concerns around gender identity. When possible, connect patients and families in need of more supportive services around gender-affirming care to appropriate specialty providers. If providers are uncertain about the current legal climate in their state, it is recommended to consult with legal counsel if needed. As pediatricians, we must strive to uphold the tenets of medicine, follow expert recommendations and guidelines based on the best available evidence to provide comprehensive care to all patients, and continue to advocate for our patients and families.
Dr. Warus is an adolescent medicine physician who specializes in care for transgender and gender-nonconforming youth, and LGBTQ health for youth at Children’s Hospital of Los Angeles. He is assistant professor of pediatrics at University of Southern California, Los Angeles.
Resources
Bright Futures – Promoting healthy development of sexuality and gender identity (Implementation tip sheet).
Rafferty J. AAP Committee on Psychosocial Aspects of Child and Family Health, AAP Committee on Adolescence, AAP Section on Lesbian, Gay, Bisexual, and Transgender Health and Wellness. Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents.
References
1. Rafferty J. AAP Committee on Psychosocial Aspects of Child and Family Health, AAP Committee on Adolescence, AAP Section on Lesbian, Gay, Bisexual, and Transgender Health and Wellness. Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents.
2. Bright Futures – Promoting healthy development of sexuality and gender identity (Implementation tip sheet).
3. Shumer DE et al. Advances in the care of transgender children and adolescents.
4. Vance SR et al. Psychological and medical care of gender nonconforming youth.
5. Ehrensaft D et al. Prepubertal social gender transitions: What we know; what we can learn – A view from a gender affirmative lens.
6. Olson KR et al. Mental health of transgender children who are supported in their identities.
7. Olson J et al. Management of the transgender adolescent.
8. Rodgers A and Goldberg M. New State laws force families with trans kids to seek gender-affirming care elsewhere.
9. Wyckoff AS, ed. AAP reaffirms gender-affirming care policy, authorizes systematic review of evidence to guide update.
As the political targeting of transgender youth and families continues to play out on the national stage, it is more important than ever for pediatricians and other primary care providers to support this vulnerable population by defending the recommendations and guidelines of reputable medical organizations based in science and to show grace and humility in caring for their patients.
Guidelines and resources
All leading medical groups in the United States with statements or policies related to gender-affirming care (including the American Medical Association, the American Academy of Pediatrics, the Society for Adolescent Health and Medicine, the Pediatric Endocrine Society, the American Academy of Child and Adolescent Psychiatry, and many more) recognize that this care is medically necessary and that exclusions for gender-related services are harmful to patients and their families. As pediatricians, families and youth rely on our expertise and guidance related to childhood and adolescent development, including the development of gender identity and ways to create safe and supportive environments needed for youth to reach their full potential.1
While pediatricians are experts in youth development, some may have had limited access to training specific to LGBTQ+ identity development and interventions related to gender-affirming care. There are, however, readily accessible resources to help guide pediatricians in providing support and recommendations to families with concerns around gender or sexuality (See Resources). The American Academy of Pediatrics and Bright Futures recommend discussing the differences between assigned sex at birth and gender identity development with parents of those younger than 12 months of age as well as beginning to discuss and explore gender identity with all youth beginning at 4-5 years of age. Beginning at 8 years of age, pediatricians are also recommended to assess for a patient’s understanding and feelings toward emerging puberty to identify any potential concerns for gender dysphoria.2 If concerns or questions emerge from screening, the family can then be referred to a gender-affirming care specialist for more support.
Gender dysphoria and gender-affirming care
Gender dysphoria may present in different ways and at different times for each patient. Some patients may present early in childhood with gender-diverse behaviors or the assertion of a gender identity different than their assigned sex at birth. However, the most commonly seen presentation is just prior to or during puberty, when one’s physical body starts to change in ways that are not consistent with their gender identity. Many patients report distress around gender before this time, but the distress that comes with the physical changes of puberty often prompts patients to reach out to parents, friends, and/or medical providers for help. Other than youth specifically disclosing their gender identity, as with any life stressors, gender dysphoria may initially present with a decline in school or social functioning, increased mood irritability, depression, or anxiety.3
The goal of support prior to puberty is for youth to grow and thrive as any other child and to not have gender dysphoria get in the way of normal development and social functioning.4 Some families will pursue social transition, the process of making changes within different areas of social interaction (such as name, pronouns, clothing, hairstyle, etc.) to decrease distress around gender. The decision of whether to pursue social transition is unique to each patient and family. The goal of this process is to allow youth to explore these changes in an effort to decrease the distress they experience in social interactions. Youth should be centered in this process and be the leader of any potential changes with parents and schools providing safe and supportive environments.5 Social transition has been shown to decrease rates of depression in gender-diverse youth to the same level as that of their cisgender peers.6
It is important to note that there are no recommended medical interventions for gender-affirming care before the time of puberty and, once a patient reaches Sexual Maturity Rating II (early puberty), the first potential treatment option is the reversible suppression of puberty using gonadotropin-releasing hormone (GnRH) analogues. The goal of this type of medication is to allow youth more time to explore their gender and avoid the permanent physical changes that occur during their endogenous puberty that can have a significant negative impact on their gender dysphoria and psychosocial functioning. Youth and their families can then later decide to discontinue the medication and go through their endogenous puberty or to proceed with gender-affirming hormone treatment.7
With the growing number of states who have or are attempting to ban gender-affirming care for youth, more patients and families will be left with no options for accessing this potentially life-saving care and support within their home state. Some families have already been forced to relocate to more supportive environments or to travel significant distances to receive medically necessary care.8 This summer, the American Academy of Pediatrics reaffirmed their current policy stating, “The AAP opposes any laws or regulations that discriminate against transgender and gender-diverse individuals, or that interfere in the doctor-patient relationship,” and they “support giving transgender adolescents access to the health care they need.”9
Pediatricians should continue to utilize existing resources for recommended routine screening and subsequent referral for patients or families with concerns around gender identity. When possible, connect patients and families in need of more supportive services around gender-affirming care to appropriate specialty providers. If providers are uncertain about the current legal climate in their state, it is recommended to consult with legal counsel if needed. As pediatricians, we must strive to uphold the tenets of medicine, follow expert recommendations and guidelines based on the best available evidence to provide comprehensive care to all patients, and continue to advocate for our patients and families.
Dr. Warus is an adolescent medicine physician who specializes in care for transgender and gender-nonconforming youth, and LGBTQ health for youth at Children’s Hospital of Los Angeles. He is assistant professor of pediatrics at University of Southern California, Los Angeles.
Resources
Bright Futures – Promoting healthy development of sexuality and gender identity (Implementation tip sheet).
Rafferty J. AAP Committee on Psychosocial Aspects of Child and Family Health, AAP Committee on Adolescence, AAP Section on Lesbian, Gay, Bisexual, and Transgender Health and Wellness. Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents.
References
1. Rafferty J. AAP Committee on Psychosocial Aspects of Child and Family Health, AAP Committee on Adolescence, AAP Section on Lesbian, Gay, Bisexual, and Transgender Health and Wellness. Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents.
2. Bright Futures – Promoting healthy development of sexuality and gender identity (Implementation tip sheet).
3. Shumer DE et al. Advances in the care of transgender children and adolescents.
4. Vance SR et al. Psychological and medical care of gender nonconforming youth.
5. Ehrensaft D et al. Prepubertal social gender transitions: What we know; what we can learn – A view from a gender affirmative lens.
6. Olson KR et al. Mental health of transgender children who are supported in their identities.
7. Olson J et al. Management of the transgender adolescent.
8. Rodgers A and Goldberg M. New State laws force families with trans kids to seek gender-affirming care elsewhere.
9. Wyckoff AS, ed. AAP reaffirms gender-affirming care policy, authorizes systematic review of evidence to guide update.
As the political targeting of transgender youth and families continues to play out on the national stage, it is more important than ever for pediatricians and other primary care providers to support this vulnerable population by defending the recommendations and guidelines of reputable medical organizations based in science and to show grace and humility in caring for their patients.
Guidelines and resources
All leading medical groups in the United States with statements or policies related to gender-affirming care (including the American Medical Association, the American Academy of Pediatrics, the Society for Adolescent Health and Medicine, the Pediatric Endocrine Society, the American Academy of Child and Adolescent Psychiatry, and many more) recognize that this care is medically necessary and that exclusions for gender-related services are harmful to patients and their families. As pediatricians, families and youth rely on our expertise and guidance related to childhood and adolescent development, including the development of gender identity and ways to create safe and supportive environments needed for youth to reach their full potential.1
While pediatricians are experts in youth development, some may have had limited access to training specific to LGBTQ+ identity development and interventions related to gender-affirming care. There are, however, readily accessible resources to help guide pediatricians in providing support and recommendations to families with concerns around gender or sexuality (See Resources). The American Academy of Pediatrics and Bright Futures recommend discussing the differences between assigned sex at birth and gender identity development with parents of those younger than 12 months of age as well as beginning to discuss and explore gender identity with all youth beginning at 4-5 years of age. Beginning at 8 years of age, pediatricians are also recommended to assess for a patient’s understanding and feelings toward emerging puberty to identify any potential concerns for gender dysphoria.2 If concerns or questions emerge from screening, the family can then be referred to a gender-affirming care specialist for more support.
Gender dysphoria and gender-affirming care
Gender dysphoria may present in different ways and at different times for each patient. Some patients may present early in childhood with gender-diverse behaviors or the assertion of a gender identity different than their assigned sex at birth. However, the most commonly seen presentation is just prior to or during puberty, when one’s physical body starts to change in ways that are not consistent with their gender identity. Many patients report distress around gender before this time, but the distress that comes with the physical changes of puberty often prompts patients to reach out to parents, friends, and/or medical providers for help. Other than youth specifically disclosing their gender identity, as with any life stressors, gender dysphoria may initially present with a decline in school or social functioning, increased mood irritability, depression, or anxiety.3
The goal of support prior to puberty is for youth to grow and thrive as any other child and to not have gender dysphoria get in the way of normal development and social functioning.4 Some families will pursue social transition, the process of making changes within different areas of social interaction (such as name, pronouns, clothing, hairstyle, etc.) to decrease distress around gender. The decision of whether to pursue social transition is unique to each patient and family. The goal of this process is to allow youth to explore these changes in an effort to decrease the distress they experience in social interactions. Youth should be centered in this process and be the leader of any potential changes with parents and schools providing safe and supportive environments.5 Social transition has been shown to decrease rates of depression in gender-diverse youth to the same level as that of their cisgender peers.6
It is important to note that there are no recommended medical interventions for gender-affirming care before the time of puberty and, once a patient reaches Sexual Maturity Rating II (early puberty), the first potential treatment option is the reversible suppression of puberty using gonadotropin-releasing hormone (GnRH) analogues. The goal of this type of medication is to allow youth more time to explore their gender and avoid the permanent physical changes that occur during their endogenous puberty that can have a significant negative impact on their gender dysphoria and psychosocial functioning. Youth and their families can then later decide to discontinue the medication and go through their endogenous puberty or to proceed with gender-affirming hormone treatment.7
With the growing number of states who have or are attempting to ban gender-affirming care for youth, more patients and families will be left with no options for accessing this potentially life-saving care and support within their home state. Some families have already been forced to relocate to more supportive environments or to travel significant distances to receive medically necessary care.8 This summer, the American Academy of Pediatrics reaffirmed their current policy stating, “The AAP opposes any laws or regulations that discriminate against transgender and gender-diverse individuals, or that interfere in the doctor-patient relationship,” and they “support giving transgender adolescents access to the health care they need.”9
Pediatricians should continue to utilize existing resources for recommended routine screening and subsequent referral for patients or families with concerns around gender identity. When possible, connect patients and families in need of more supportive services around gender-affirming care to appropriate specialty providers. If providers are uncertain about the current legal climate in their state, it is recommended to consult with legal counsel if needed. As pediatricians, we must strive to uphold the tenets of medicine, follow expert recommendations and guidelines based on the best available evidence to provide comprehensive care to all patients, and continue to advocate for our patients and families.
Dr. Warus is an adolescent medicine physician who specializes in care for transgender and gender-nonconforming youth, and LGBTQ health for youth at Children’s Hospital of Los Angeles. He is assistant professor of pediatrics at University of Southern California, Los Angeles.
Resources
Bright Futures – Promoting healthy development of sexuality and gender identity (Implementation tip sheet).
Rafferty J. AAP Committee on Psychosocial Aspects of Child and Family Health, AAP Committee on Adolescence, AAP Section on Lesbian, Gay, Bisexual, and Transgender Health and Wellness. Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents.
References
1. Rafferty J. AAP Committee on Psychosocial Aspects of Child and Family Health, AAP Committee on Adolescence, AAP Section on Lesbian, Gay, Bisexual, and Transgender Health and Wellness. Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents.
2. Bright Futures – Promoting healthy development of sexuality and gender identity (Implementation tip sheet).
3. Shumer DE et al. Advances in the care of transgender children and adolescents.
4. Vance SR et al. Psychological and medical care of gender nonconforming youth.
5. Ehrensaft D et al. Prepubertal social gender transitions: What we know; what we can learn – A view from a gender affirmative lens.
6. Olson KR et al. Mental health of transgender children who are supported in their identities.
7. Olson J et al. Management of the transgender adolescent.
8. Rodgers A and Goldberg M. New State laws force families with trans kids to seek gender-affirming care elsewhere.
9. Wyckoff AS, ed. AAP reaffirms gender-affirming care policy, authorizes systematic review of evidence to guide update.
New evidence suggests genetic risk factors in hidradenitis suppurativa
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with lesions that include deep-seated nodules and abscesses, draining tracts, and fibrotic scars, and has been reported to be highly heritable.
A genomewide association study (GWAS) that involved a meta-analysis of data from three large biobanks (UK Biobank, FinnGen, and BioVU) identified one significant locus and two suggestive loci. The researchers were able to replicate the association with HS for two loci near the SOX9 and KLF5 genes in BioVU.
In addition, they also looked at genetic correlations between HS and autoimmune and inflammatory diseases, and results suggested a positive association with inflammatory bowel disease, psoriasis, and type 2 diabetes.
However, while plausible, the variant associations near candidate genes do not prove a causal effect of these variants or genes on disease risk, and further study is needed.
“It’s possible that these genes aren’t the ones affected by the variations we describe, but both are very strong candidates,” said study author Christopher J. Sayed, MD, associate professor of dermatology, University of North Carolina at Chapel Hill. “This improves our understanding of HS as a disease that is likely related to genetic changes that result in dysregulated hair follicle maintenance, inflammation, and wound healing.”
In turn, this will allow clinicians to educate patients about the underlying genetic influences on HS, he explained, as opposed to stigmatizing misconceptions focusing only on weight, smoking, and hygiene.
“Larger studies are underway and will be needed to find variants that may predict things like disease severity and response to treatment, but this is a big first step in the right direction,” Dr. Sayed added.
The study was published online in JAMA Dermatology.
Loci identified
GWASs have been limited in HS, and previous research has not identified significant risk loci. In the current study, Dr. Sayed and colleagues sought to identify underlying genes and genetic mechanisms that may underlie pathogenesis in HS.
They performed a GWAS in a cohort of 720 patients who were part of the Hidradenitis Suppurativa Program for Research and Care Excellence (HS ProCARE) at the UNC department of dermatology, and controls from the National Longitudinal Study of Adolescent to Adult Health (Add Health) study, a U.S.-based study following adolescents through adulthood.
The UK Biobank (UKB) is a prospective biobank with about 500,000 individuals aged 40-69 years, and FinnGen collects and analyzes genome and health data from Finnish biobank participants. To increase power to detect associations, a GWAS was performed using participants from the UKB (247 HS cases, 453,048 controls). The HS ProCARE GWAS results were meta-analyzed with UKB, along with data from FinnGen (673 HS cases, 297,544 controls). This three-way meta-analysis revealed one genomewide significant locus and two suggestive loci.
The authors found that the most strongly associated variant, rs10512572 located on chromosome 17, showed the strongest association in FinnGen; at the second locus, the most strongly associated variant was rs17090189 located on chromosome 13 and also showed the strongest association in FinnGen; and at the third locus, the most strongly associated variant, rs5792315, located on chromosome 11, showed the strongest association in HS ProCARE.
Next, they tested the 10 most strongly associated variants at the three loci in the BioVU biobank, which has 290 HS cases, including 189 individuals of European ancestry and 101 individuals of African ancestry, with 64,234 and 12,105 controls, respectively. The locus on chromosome 17 was replicated in BioVU in the same direction of effect, while one variant at the chromosome 13 locus showed nominal evidence of association in the same direction.
In a four-way meta-analysis of BioVU combined with the other three studies, the chromosome locus became more significant and the chromosome 13 locus exceeded the genomewide significance threshold. In contrast, the chromosome 11 locus was not replicated in BioVU (P = .27).
The authors pointed out that variants at these loci are located in keratinocyte regulatory elements near the genes SOX9 and KLF5, which play a role in skin and follicular inflammation, but have not previously been associated with HS pathogenesis.
Finally, they looked to see if there were shared genetic components between HS and autoimmune and inflammatory diseases. A nominally significant genetic correlation was observed between HS and inflammatory bowel disease (P = .04), psoriasis (P = .03), and type 2 diabetes (P = .04), although none reached significance.
Different manifestation with genetic variant
In a related study, researchers assessed the prevalence of the NCSTN:c.671_682del variant among individuals with HS in Malta, the island country in the Mediterranean, which has a high prevalence of HS and its associated risk factors, particularly obesity.
Led by Dillon Mintoff, MD, of the department of pathology at the University of Malta, Msida, they conducted a cross-sectional study of 113 adults with HS. In this group, 14 (12.39%) were found to be heterozygous for the NCSTN:c.671_682del variant. Individuals who had this variant were more likely to develop symptoms earlier and to manifest them in atypical skin sites, including the scalp, neck, torso, and antecubital fossae. Additionally, even though their symptoms weren’t more severe than those without the variant, patients with the variant were more likely to require treatment with biologic agents.
Studies move genetics in HS forward
Writing in an accompanying editorial, Atlas Khan, PhD, and Lynn Petukhova, PhD, from Columbia University, New York, noted that both of these HS genetic studies “set a solid foundation for future studies aimed at understanding the biological and clinical relevance of new HS genetic evidence.”
“Each study suggests a series of experiments that will allow us to gain new knowledge about HS,” they wrote, including coming closer to providing patients with a genetic diagnosis.
In addition, evidence from the GWAS paper suggests that with “larger HS GWASs we will be able to better prioritize drug-repurposing studies,” concluded the editorialists. “Both of these goals will help to improve health outcomes for patients with HS and their family members.”
Dr. Sayed reported grants and/or personal fees from AbbVie, Novartis, UCB, Incyte, InflaRx, Alumis, and ChemoCentryx outside the submitted work; and serving as a volunteer member of the board of the HS Foundation and member of the European HS Foundation. The study in Malta was funded by the Government of Malta’s Tertiary Education Scholarship Scheme and Institutional Funds from the University of Malta. Dr. Mintoff reported grants from the Government of Malta Ministry for Education, Sport, Youth, Research and Innovation during the conduct of the study. Dr. Khan reported receiving grants from the National Institute of Diabetes and Digestive Kidney Diseases. Dr. Petukhova reported receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Columbia University’s Precision Medicine Initiative, Herbert Irving Comprehensive Cancer Center, and Data Science Institute.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with lesions that include deep-seated nodules and abscesses, draining tracts, and fibrotic scars, and has been reported to be highly heritable.
A genomewide association study (GWAS) that involved a meta-analysis of data from three large biobanks (UK Biobank, FinnGen, and BioVU) identified one significant locus and two suggestive loci. The researchers were able to replicate the association with HS for two loci near the SOX9 and KLF5 genes in BioVU.
In addition, they also looked at genetic correlations between HS and autoimmune and inflammatory diseases, and results suggested a positive association with inflammatory bowel disease, psoriasis, and type 2 diabetes.
However, while plausible, the variant associations near candidate genes do not prove a causal effect of these variants or genes on disease risk, and further study is needed.
“It’s possible that these genes aren’t the ones affected by the variations we describe, but both are very strong candidates,” said study author Christopher J. Sayed, MD, associate professor of dermatology, University of North Carolina at Chapel Hill. “This improves our understanding of HS as a disease that is likely related to genetic changes that result in dysregulated hair follicle maintenance, inflammation, and wound healing.”
In turn, this will allow clinicians to educate patients about the underlying genetic influences on HS, he explained, as opposed to stigmatizing misconceptions focusing only on weight, smoking, and hygiene.
“Larger studies are underway and will be needed to find variants that may predict things like disease severity and response to treatment, but this is a big first step in the right direction,” Dr. Sayed added.
The study was published online in JAMA Dermatology.
Loci identified
GWASs have been limited in HS, and previous research has not identified significant risk loci. In the current study, Dr. Sayed and colleagues sought to identify underlying genes and genetic mechanisms that may underlie pathogenesis in HS.
They performed a GWAS in a cohort of 720 patients who were part of the Hidradenitis Suppurativa Program for Research and Care Excellence (HS ProCARE) at the UNC department of dermatology, and controls from the National Longitudinal Study of Adolescent to Adult Health (Add Health) study, a U.S.-based study following adolescents through adulthood.
The UK Biobank (UKB) is a prospective biobank with about 500,000 individuals aged 40-69 years, and FinnGen collects and analyzes genome and health data from Finnish biobank participants. To increase power to detect associations, a GWAS was performed using participants from the UKB (247 HS cases, 453,048 controls). The HS ProCARE GWAS results were meta-analyzed with UKB, along with data from FinnGen (673 HS cases, 297,544 controls). This three-way meta-analysis revealed one genomewide significant locus and two suggestive loci.
The authors found that the most strongly associated variant, rs10512572 located on chromosome 17, showed the strongest association in FinnGen; at the second locus, the most strongly associated variant was rs17090189 located on chromosome 13 and also showed the strongest association in FinnGen; and at the third locus, the most strongly associated variant, rs5792315, located on chromosome 11, showed the strongest association in HS ProCARE.
Next, they tested the 10 most strongly associated variants at the three loci in the BioVU biobank, which has 290 HS cases, including 189 individuals of European ancestry and 101 individuals of African ancestry, with 64,234 and 12,105 controls, respectively. The locus on chromosome 17 was replicated in BioVU in the same direction of effect, while one variant at the chromosome 13 locus showed nominal evidence of association in the same direction.
In a four-way meta-analysis of BioVU combined with the other three studies, the chromosome locus became more significant and the chromosome 13 locus exceeded the genomewide significance threshold. In contrast, the chromosome 11 locus was not replicated in BioVU (P = .27).
The authors pointed out that variants at these loci are located in keratinocyte regulatory elements near the genes SOX9 and KLF5, which play a role in skin and follicular inflammation, but have not previously been associated with HS pathogenesis.
Finally, they looked to see if there were shared genetic components between HS and autoimmune and inflammatory diseases. A nominally significant genetic correlation was observed between HS and inflammatory bowel disease (P = .04), psoriasis (P = .03), and type 2 diabetes (P = .04), although none reached significance.
Different manifestation with genetic variant
In a related study, researchers assessed the prevalence of the NCSTN:c.671_682del variant among individuals with HS in Malta, the island country in the Mediterranean, which has a high prevalence of HS and its associated risk factors, particularly obesity.
Led by Dillon Mintoff, MD, of the department of pathology at the University of Malta, Msida, they conducted a cross-sectional study of 113 adults with HS. In this group, 14 (12.39%) were found to be heterozygous for the NCSTN:c.671_682del variant. Individuals who had this variant were more likely to develop symptoms earlier and to manifest them in atypical skin sites, including the scalp, neck, torso, and antecubital fossae. Additionally, even though their symptoms weren’t more severe than those without the variant, patients with the variant were more likely to require treatment with biologic agents.
Studies move genetics in HS forward
Writing in an accompanying editorial, Atlas Khan, PhD, and Lynn Petukhova, PhD, from Columbia University, New York, noted that both of these HS genetic studies “set a solid foundation for future studies aimed at understanding the biological and clinical relevance of new HS genetic evidence.”
“Each study suggests a series of experiments that will allow us to gain new knowledge about HS,” they wrote, including coming closer to providing patients with a genetic diagnosis.
In addition, evidence from the GWAS paper suggests that with “larger HS GWASs we will be able to better prioritize drug-repurposing studies,” concluded the editorialists. “Both of these goals will help to improve health outcomes for patients with HS and their family members.”
Dr. Sayed reported grants and/or personal fees from AbbVie, Novartis, UCB, Incyte, InflaRx, Alumis, and ChemoCentryx outside the submitted work; and serving as a volunteer member of the board of the HS Foundation and member of the European HS Foundation. The study in Malta was funded by the Government of Malta’s Tertiary Education Scholarship Scheme and Institutional Funds from the University of Malta. Dr. Mintoff reported grants from the Government of Malta Ministry for Education, Sport, Youth, Research and Innovation during the conduct of the study. Dr. Khan reported receiving grants from the National Institute of Diabetes and Digestive Kidney Diseases. Dr. Petukhova reported receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Columbia University’s Precision Medicine Initiative, Herbert Irving Comprehensive Cancer Center, and Data Science Institute.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with lesions that include deep-seated nodules and abscesses, draining tracts, and fibrotic scars, and has been reported to be highly heritable.
A genomewide association study (GWAS) that involved a meta-analysis of data from three large biobanks (UK Biobank, FinnGen, and BioVU) identified one significant locus and two suggestive loci. The researchers were able to replicate the association with HS for two loci near the SOX9 and KLF5 genes in BioVU.
In addition, they also looked at genetic correlations between HS and autoimmune and inflammatory diseases, and results suggested a positive association with inflammatory bowel disease, psoriasis, and type 2 diabetes.
However, while plausible, the variant associations near candidate genes do not prove a causal effect of these variants or genes on disease risk, and further study is needed.
“It’s possible that these genes aren’t the ones affected by the variations we describe, but both are very strong candidates,” said study author Christopher J. Sayed, MD, associate professor of dermatology, University of North Carolina at Chapel Hill. “This improves our understanding of HS as a disease that is likely related to genetic changes that result in dysregulated hair follicle maintenance, inflammation, and wound healing.”
In turn, this will allow clinicians to educate patients about the underlying genetic influences on HS, he explained, as opposed to stigmatizing misconceptions focusing only on weight, smoking, and hygiene.
“Larger studies are underway and will be needed to find variants that may predict things like disease severity and response to treatment, but this is a big first step in the right direction,” Dr. Sayed added.
The study was published online in JAMA Dermatology.
Loci identified
GWASs have been limited in HS, and previous research has not identified significant risk loci. In the current study, Dr. Sayed and colleagues sought to identify underlying genes and genetic mechanisms that may underlie pathogenesis in HS.
They performed a GWAS in a cohort of 720 patients who were part of the Hidradenitis Suppurativa Program for Research and Care Excellence (HS ProCARE) at the UNC department of dermatology, and controls from the National Longitudinal Study of Adolescent to Adult Health (Add Health) study, a U.S.-based study following adolescents through adulthood.
The UK Biobank (UKB) is a prospective biobank with about 500,000 individuals aged 40-69 years, and FinnGen collects and analyzes genome and health data from Finnish biobank participants. To increase power to detect associations, a GWAS was performed using participants from the UKB (247 HS cases, 453,048 controls). The HS ProCARE GWAS results were meta-analyzed with UKB, along with data from FinnGen (673 HS cases, 297,544 controls). This three-way meta-analysis revealed one genomewide significant locus and two suggestive loci.
The authors found that the most strongly associated variant, rs10512572 located on chromosome 17, showed the strongest association in FinnGen; at the second locus, the most strongly associated variant was rs17090189 located on chromosome 13 and also showed the strongest association in FinnGen; and at the third locus, the most strongly associated variant, rs5792315, located on chromosome 11, showed the strongest association in HS ProCARE.
Next, they tested the 10 most strongly associated variants at the three loci in the BioVU biobank, which has 290 HS cases, including 189 individuals of European ancestry and 101 individuals of African ancestry, with 64,234 and 12,105 controls, respectively. The locus on chromosome 17 was replicated in BioVU in the same direction of effect, while one variant at the chromosome 13 locus showed nominal evidence of association in the same direction.
In a four-way meta-analysis of BioVU combined with the other three studies, the chromosome locus became more significant and the chromosome 13 locus exceeded the genomewide significance threshold. In contrast, the chromosome 11 locus was not replicated in BioVU (P = .27).
The authors pointed out that variants at these loci are located in keratinocyte regulatory elements near the genes SOX9 and KLF5, which play a role in skin and follicular inflammation, but have not previously been associated with HS pathogenesis.
Finally, they looked to see if there were shared genetic components between HS and autoimmune and inflammatory diseases. A nominally significant genetic correlation was observed between HS and inflammatory bowel disease (P = .04), psoriasis (P = .03), and type 2 diabetes (P = .04), although none reached significance.
Different manifestation with genetic variant
In a related study, researchers assessed the prevalence of the NCSTN:c.671_682del variant among individuals with HS in Malta, the island country in the Mediterranean, which has a high prevalence of HS and its associated risk factors, particularly obesity.
Led by Dillon Mintoff, MD, of the department of pathology at the University of Malta, Msida, they conducted a cross-sectional study of 113 adults with HS. In this group, 14 (12.39%) were found to be heterozygous for the NCSTN:c.671_682del variant. Individuals who had this variant were more likely to develop symptoms earlier and to manifest them in atypical skin sites, including the scalp, neck, torso, and antecubital fossae. Additionally, even though their symptoms weren’t more severe than those without the variant, patients with the variant were more likely to require treatment with biologic agents.
Studies move genetics in HS forward
Writing in an accompanying editorial, Atlas Khan, PhD, and Lynn Petukhova, PhD, from Columbia University, New York, noted that both of these HS genetic studies “set a solid foundation for future studies aimed at understanding the biological and clinical relevance of new HS genetic evidence.”
“Each study suggests a series of experiments that will allow us to gain new knowledge about HS,” they wrote, including coming closer to providing patients with a genetic diagnosis.
In addition, evidence from the GWAS paper suggests that with “larger HS GWASs we will be able to better prioritize drug-repurposing studies,” concluded the editorialists. “Both of these goals will help to improve health outcomes for patients with HS and their family members.”
Dr. Sayed reported grants and/or personal fees from AbbVie, Novartis, UCB, Incyte, InflaRx, Alumis, and ChemoCentryx outside the submitted work; and serving as a volunteer member of the board of the HS Foundation and member of the European HS Foundation. The study in Malta was funded by the Government of Malta’s Tertiary Education Scholarship Scheme and Institutional Funds from the University of Malta. Dr. Mintoff reported grants from the Government of Malta Ministry for Education, Sport, Youth, Research and Innovation during the conduct of the study. Dr. Khan reported receiving grants from the National Institute of Diabetes and Digestive Kidney Diseases. Dr. Petukhova reported receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Columbia University’s Precision Medicine Initiative, Herbert Irving Comprehensive Cancer Center, and Data Science Institute.
FROM JAMA DERMATOLOGY
ADHD meds cut hospitalization risk in borderline personality disorder patients
Although most patients with borderline personality disorder (BPD) receive psychopharmacological treatment, clinical guidance and outcomes data for specific medication use in these patients are lacking, wrote Johannes Lieslehto, MD, PhD, of the University of Eastern Finland, Niuvankuja, and colleagues.
In a study published in Acta Psychiatrica Scandinavica , the researchers – using national databases in Sweden – identified 17,532 adults with BPD who were treated with medications between 2006 and 2018.
Medications included benzodiazepines, antipsychotics, and antidepressants, as well as medications often used for ADHD: clozapine, lisdexamphetamine, bupropion, and methylphenidate. The mean age of the study population was 29.8 years and 2,649 were men.
The primary outcomes were psychiatric hospitalization (which served as an indication of treatment failure), all-cause hospitalization, or death.
Overall, treatment with benzodiazepines, antipsychotics, and antidepressants was associated with increased risk of psychiatric rehospitalization, with hazard ratios of 1.38, 1.19, and 1.18, respectively, and with increased risk of all-cause hospitalization or death (HR 1.37, HR 1.21, HR 1.17, respectively).
By contrast, treatment with ADHD medication was associated with decreased risk of psychiatric hospitalization (HR = 0.88), as well as a decreased risk of all-cause hospitalization or death (HR = 0.86).
Specifically, clozapine, lisdexamphetamine, bupropion, and methylphenidate were associated with decreased risk of psychiatric rehospitalization, with hazard ratios of 0.54, 0.79, 0.84, and 0.90, respectively.
Treatment with mood stabilizers had no significant impact on outcomes.
BPD patients treated with ADHD medications also may exhibit ADHD symptoms, the researchers wrote in their discussion. However, “Although BPD and ADHD partially overlap in symptoms such as impulsivity and emotion dysregulation, previous efforts to investigate the efficacy of ADHD medication treatment in BPD are scarce,” and randomized, controlled trials are needed to determine whether these medications should be given to BPD patients without comorbid ADHD symptoms, they said.
The findings were limited by several factors including the lack of clinical parameters on symptom severity, quality of life, and level of function, and premature prescribing of medication (protopathic bias) may have affected the results, the researchers noted.
The results were strengthened by the large sample size and long follow-up, which increases the generalizability to real-world patients, and suggest that many pharmacological treatments for BPD may not improve outcomes, the researchers said. However, “even in the presence of possible protopathic bias, treatment with lisdexamphetamine, bupropion, methylphenidate, and clozapine was associated with improved outcomes, encouraging further research on these treatments,” they said.
The study was supported by the Finnish Ministry of Social Affairs and Health and the Academy of Finland. Dr. Lieslehto had no financial conflicts to disclose.
Although most patients with borderline personality disorder (BPD) receive psychopharmacological treatment, clinical guidance and outcomes data for specific medication use in these patients are lacking, wrote Johannes Lieslehto, MD, PhD, of the University of Eastern Finland, Niuvankuja, and colleagues.
In a study published in Acta Psychiatrica Scandinavica , the researchers – using national databases in Sweden – identified 17,532 adults with BPD who were treated with medications between 2006 and 2018.
Medications included benzodiazepines, antipsychotics, and antidepressants, as well as medications often used for ADHD: clozapine, lisdexamphetamine, bupropion, and methylphenidate. The mean age of the study population was 29.8 years and 2,649 were men.
The primary outcomes were psychiatric hospitalization (which served as an indication of treatment failure), all-cause hospitalization, or death.
Overall, treatment with benzodiazepines, antipsychotics, and antidepressants was associated with increased risk of psychiatric rehospitalization, with hazard ratios of 1.38, 1.19, and 1.18, respectively, and with increased risk of all-cause hospitalization or death (HR 1.37, HR 1.21, HR 1.17, respectively).
By contrast, treatment with ADHD medication was associated with decreased risk of psychiatric hospitalization (HR = 0.88), as well as a decreased risk of all-cause hospitalization or death (HR = 0.86).
Specifically, clozapine, lisdexamphetamine, bupropion, and methylphenidate were associated with decreased risk of psychiatric rehospitalization, with hazard ratios of 0.54, 0.79, 0.84, and 0.90, respectively.
Treatment with mood stabilizers had no significant impact on outcomes.
BPD patients treated with ADHD medications also may exhibit ADHD symptoms, the researchers wrote in their discussion. However, “Although BPD and ADHD partially overlap in symptoms such as impulsivity and emotion dysregulation, previous efforts to investigate the efficacy of ADHD medication treatment in BPD are scarce,” and randomized, controlled trials are needed to determine whether these medications should be given to BPD patients without comorbid ADHD symptoms, they said.
The findings were limited by several factors including the lack of clinical parameters on symptom severity, quality of life, and level of function, and premature prescribing of medication (protopathic bias) may have affected the results, the researchers noted.
The results were strengthened by the large sample size and long follow-up, which increases the generalizability to real-world patients, and suggest that many pharmacological treatments for BPD may not improve outcomes, the researchers said. However, “even in the presence of possible protopathic bias, treatment with lisdexamphetamine, bupropion, methylphenidate, and clozapine was associated with improved outcomes, encouraging further research on these treatments,” they said.
The study was supported by the Finnish Ministry of Social Affairs and Health and the Academy of Finland. Dr. Lieslehto had no financial conflicts to disclose.
Although most patients with borderline personality disorder (BPD) receive psychopharmacological treatment, clinical guidance and outcomes data for specific medication use in these patients are lacking, wrote Johannes Lieslehto, MD, PhD, of the University of Eastern Finland, Niuvankuja, and colleagues.
In a study published in Acta Psychiatrica Scandinavica , the researchers – using national databases in Sweden – identified 17,532 adults with BPD who were treated with medications between 2006 and 2018.
Medications included benzodiazepines, antipsychotics, and antidepressants, as well as medications often used for ADHD: clozapine, lisdexamphetamine, bupropion, and methylphenidate. The mean age of the study population was 29.8 years and 2,649 were men.
The primary outcomes were psychiatric hospitalization (which served as an indication of treatment failure), all-cause hospitalization, or death.
Overall, treatment with benzodiazepines, antipsychotics, and antidepressants was associated with increased risk of psychiatric rehospitalization, with hazard ratios of 1.38, 1.19, and 1.18, respectively, and with increased risk of all-cause hospitalization or death (HR 1.37, HR 1.21, HR 1.17, respectively).
By contrast, treatment with ADHD medication was associated with decreased risk of psychiatric hospitalization (HR = 0.88), as well as a decreased risk of all-cause hospitalization or death (HR = 0.86).
Specifically, clozapine, lisdexamphetamine, bupropion, and methylphenidate were associated with decreased risk of psychiatric rehospitalization, with hazard ratios of 0.54, 0.79, 0.84, and 0.90, respectively.
Treatment with mood stabilizers had no significant impact on outcomes.
BPD patients treated with ADHD medications also may exhibit ADHD symptoms, the researchers wrote in their discussion. However, “Although BPD and ADHD partially overlap in symptoms such as impulsivity and emotion dysregulation, previous efforts to investigate the efficacy of ADHD medication treatment in BPD are scarce,” and randomized, controlled trials are needed to determine whether these medications should be given to BPD patients without comorbid ADHD symptoms, they said.
The findings were limited by several factors including the lack of clinical parameters on symptom severity, quality of life, and level of function, and premature prescribing of medication (protopathic bias) may have affected the results, the researchers noted.
The results were strengthened by the large sample size and long follow-up, which increases the generalizability to real-world patients, and suggest that many pharmacological treatments for BPD may not improve outcomes, the researchers said. However, “even in the presence of possible protopathic bias, treatment with lisdexamphetamine, bupropion, methylphenidate, and clozapine was associated with improved outcomes, encouraging further research on these treatments,” they said.
The study was supported by the Finnish Ministry of Social Affairs and Health and the Academy of Finland. Dr. Lieslehto had no financial conflicts to disclose.
FROM ACTA PSYCHIATRICA SCANDINAVICA
Landmark obesity legislation reintroduced in Congress
The AGA Government Affairs Committee is pleased to announce the Senate and House have reintroduced the bipartisan Treat and Reduce Obesity Act (TROA) (H.R. 4818/S. 2407). This legislation is a vital first step in expanding access to obesity treatment. If passed, the bill would expand Medicare coverage to include screening and treatment of obesity by health care providers who provide obesity care. The bill also includes coverage of behavioral counseling, prescription drugs for long-term weight management, and other prevention and treatment options.
The passage of TROA could lead to improved obesity care options for all Americans since many private insurance companies model their covered health benefits to reflect Medicare.
The AGA Government Affairs Committee is pleased to announce the Senate and House have reintroduced the bipartisan Treat and Reduce Obesity Act (TROA) (H.R. 4818/S. 2407). This legislation is a vital first step in expanding access to obesity treatment. If passed, the bill would expand Medicare coverage to include screening and treatment of obesity by health care providers who provide obesity care. The bill also includes coverage of behavioral counseling, prescription drugs for long-term weight management, and other prevention and treatment options.
The passage of TROA could lead to improved obesity care options for all Americans since many private insurance companies model their covered health benefits to reflect Medicare.
The AGA Government Affairs Committee is pleased to announce the Senate and House have reintroduced the bipartisan Treat and Reduce Obesity Act (TROA) (H.R. 4818/S. 2407). This legislation is a vital first step in expanding access to obesity treatment. If passed, the bill would expand Medicare coverage to include screening and treatment of obesity by health care providers who provide obesity care. The bill also includes coverage of behavioral counseling, prescription drugs for long-term weight management, and other prevention and treatment options.
The passage of TROA could lead to improved obesity care options for all Americans since many private insurance companies model their covered health benefits to reflect Medicare.
Cardiometabolic multimorbidity positively impacts secukinumab treatment persistence in PsA
Key clinical point: The presence of cardiometabolic multimorbidity may be associated with an improved treatment persistence with secukinumab in patients with psoriatic arthritis (PsA).
Major finding: The cumulative 60-month drug retention rate for secukinumab was 57.0% in patients with cardiometabolic multimorbidity (P = .042). Those with type 2 diabetes had a significantly better drug retention rate than those without (P = .044).
Study details: Findings are from a retrospective study of prospectively followed-up patients with PsA (n = 207) who received secukinumab for at least 3 months.
Disclosures: The study did not disclose the source of funding. The authors declared no conflicts of interest.
Source: Ruscitti P et al. The assessment of the drug retention rate of secukinumab in patients with psoriatic arthritis in a real-life multicentre cohort. Clin Exp Rheumatol. 2023 (Jul 24). doi: 10.55563/clinexprheumatol/tpp63h
Key clinical point: The presence of cardiometabolic multimorbidity may be associated with an improved treatment persistence with secukinumab in patients with psoriatic arthritis (PsA).
Major finding: The cumulative 60-month drug retention rate for secukinumab was 57.0% in patients with cardiometabolic multimorbidity (P = .042). Those with type 2 diabetes had a significantly better drug retention rate than those without (P = .044).
Study details: Findings are from a retrospective study of prospectively followed-up patients with PsA (n = 207) who received secukinumab for at least 3 months.
Disclosures: The study did not disclose the source of funding. The authors declared no conflicts of interest.
Source: Ruscitti P et al. The assessment of the drug retention rate of secukinumab in patients with psoriatic arthritis in a real-life multicentre cohort. Clin Exp Rheumatol. 2023 (Jul 24). doi: 10.55563/clinexprheumatol/tpp63h
Key clinical point: The presence of cardiometabolic multimorbidity may be associated with an improved treatment persistence with secukinumab in patients with psoriatic arthritis (PsA).
Major finding: The cumulative 60-month drug retention rate for secukinumab was 57.0% in patients with cardiometabolic multimorbidity (P = .042). Those with type 2 diabetes had a significantly better drug retention rate than those without (P = .044).
Study details: Findings are from a retrospective study of prospectively followed-up patients with PsA (n = 207) who received secukinumab for at least 3 months.
Disclosures: The study did not disclose the source of funding. The authors declared no conflicts of interest.
Source: Ruscitti P et al. The assessment of the drug retention rate of secukinumab in patients with psoriatic arthritis in a real-life multicentre cohort. Clin Exp Rheumatol. 2023 (Jul 24). doi: 10.55563/clinexprheumatol/tpp63h
Real-world study confirms efficacy and longer treatment persistence with ixekizumab
Key clinical point: In the real-world setting, ixekizumab showed improvements in disease activity and treatment persistence in patients with psoriatic arthritis (PsA) with long-standing disease.
Major finding: The mean time of ixekizumab persistence was 86.9 weeks with the persistence rates at 24, 48, and 104 weeks being 95.5%, 84.3%, and 68.5%, respectively. The Disease Activity in Psoriatic Arthritis score reduced significantly from 23.7 at baseline to 14.8 (P = .005) and 14.3 (P = .004) at 12 and 24 weeks, respectively, of ixekizumab treatment.
Study details: Findings are from an observational, retrospective longitudinal study including 89 adult patients with PsA who initiated ixekizumab.
Disclosures: This study was funded by Eli Lilly & Co. Three authors declared being employees of Lilly and two authors reported employment with a consulting company funded by Lilly. Five authors reported ties with various sources, including Lilly. Other authors declared no conflicts of interest.
Source: Joven B et al. Persistence and use of Ixekizumab in patients with psoriatic arthritis in real-world practice in Spain. The PRO-STIP Study. Rheumatol Ther. 2023 (Jul 23). doi: 10.1007/s40744-023-00584-8
Key clinical point: In the real-world setting, ixekizumab showed improvements in disease activity and treatment persistence in patients with psoriatic arthritis (PsA) with long-standing disease.
Major finding: The mean time of ixekizumab persistence was 86.9 weeks with the persistence rates at 24, 48, and 104 weeks being 95.5%, 84.3%, and 68.5%, respectively. The Disease Activity in Psoriatic Arthritis score reduced significantly from 23.7 at baseline to 14.8 (P = .005) and 14.3 (P = .004) at 12 and 24 weeks, respectively, of ixekizumab treatment.
Study details: Findings are from an observational, retrospective longitudinal study including 89 adult patients with PsA who initiated ixekizumab.
Disclosures: This study was funded by Eli Lilly & Co. Three authors declared being employees of Lilly and two authors reported employment with a consulting company funded by Lilly. Five authors reported ties with various sources, including Lilly. Other authors declared no conflicts of interest.
Source: Joven B et al. Persistence and use of Ixekizumab in patients with psoriatic arthritis in real-world practice in Spain. The PRO-STIP Study. Rheumatol Ther. 2023 (Jul 23). doi: 10.1007/s40744-023-00584-8
Key clinical point: In the real-world setting, ixekizumab showed improvements in disease activity and treatment persistence in patients with psoriatic arthritis (PsA) with long-standing disease.
Major finding: The mean time of ixekizumab persistence was 86.9 weeks with the persistence rates at 24, 48, and 104 weeks being 95.5%, 84.3%, and 68.5%, respectively. The Disease Activity in Psoriatic Arthritis score reduced significantly from 23.7 at baseline to 14.8 (P = .005) and 14.3 (P = .004) at 12 and 24 weeks, respectively, of ixekizumab treatment.
Study details: Findings are from an observational, retrospective longitudinal study including 89 adult patients with PsA who initiated ixekizumab.
Disclosures: This study was funded by Eli Lilly & Co. Three authors declared being employees of Lilly and two authors reported employment with a consulting company funded by Lilly. Five authors reported ties with various sources, including Lilly. Other authors declared no conflicts of interest.
Source: Joven B et al. Persistence and use of Ixekizumab in patients with psoriatic arthritis in real-world practice in Spain. The PRO-STIP Study. Rheumatol Ther. 2023 (Jul 23). doi: 10.1007/s40744-023-00584-8
Differential synovial and serum B-cell signatures between autoantibody-negative and autoantibody-positive RA
Key clinical point: Synovial and serum B-lymphocyte involvement differ between autoantibody-positive and autoantibody-negative rheumatoid arthritis (RA), with autoantibody-negative RA closely resembling that in polyarticular psoriatic arthritis (PsA).
Major finding: The CD20+ B-cell aggregational score was significantly lower in autoantibody-negative RA than in autoantibody-positive RA (mean 1.8 vs 2.4; P = .03) but comparable to that of polyarticular PsA (P = .78). The frequency of lympho-myeloid synovitis was lower in autoantibody-negative RA than in autoantibody-positive RA (38.2% vs 62.9%; P = .07) but comparable to that of polyarticular PsA (P = .8).
Study details: This study included 131 patients who underwent synovial biopsy and were categorized into those having autoantibody-positive RA (n = 43), autoantibody-negative RA (n = 35), symmetric polyarticular PsA (n = 25), and asymmetric oligoarticular PsA (n = 28).
Disclosures: This study was supported by IRCCS Policlinico San Matteo Foundation, Pavia, Italy. C Montecucco and S Bugatti reported receiving grants or research support and personal fees from various sources. The remaining authors declared no conflicts of interest.
Source: De Stefano L et al. Synovial and serum B-cell signature of autoantibody-negative rheumatoid arthritis versus autoantibody-positive rheumatoid arthritis and psoriatic arthritis. Rheumatology (Oxford). 2023 (Jul 22). doi: 10.1093/rheumatology/kead378
Key clinical point: Synovial and serum B-lymphocyte involvement differ between autoantibody-positive and autoantibody-negative rheumatoid arthritis (RA), with autoantibody-negative RA closely resembling that in polyarticular psoriatic arthritis (PsA).
Major finding: The CD20+ B-cell aggregational score was significantly lower in autoantibody-negative RA than in autoantibody-positive RA (mean 1.8 vs 2.4; P = .03) but comparable to that of polyarticular PsA (P = .78). The frequency of lympho-myeloid synovitis was lower in autoantibody-negative RA than in autoantibody-positive RA (38.2% vs 62.9%; P = .07) but comparable to that of polyarticular PsA (P = .8).
Study details: This study included 131 patients who underwent synovial biopsy and were categorized into those having autoantibody-positive RA (n = 43), autoantibody-negative RA (n = 35), symmetric polyarticular PsA (n = 25), and asymmetric oligoarticular PsA (n = 28).
Disclosures: This study was supported by IRCCS Policlinico San Matteo Foundation, Pavia, Italy. C Montecucco and S Bugatti reported receiving grants or research support and personal fees from various sources. The remaining authors declared no conflicts of interest.
Source: De Stefano L et al. Synovial and serum B-cell signature of autoantibody-negative rheumatoid arthritis versus autoantibody-positive rheumatoid arthritis and psoriatic arthritis. Rheumatology (Oxford). 2023 (Jul 22). doi: 10.1093/rheumatology/kead378
Key clinical point: Synovial and serum B-lymphocyte involvement differ between autoantibody-positive and autoantibody-negative rheumatoid arthritis (RA), with autoantibody-negative RA closely resembling that in polyarticular psoriatic arthritis (PsA).
Major finding: The CD20+ B-cell aggregational score was significantly lower in autoantibody-negative RA than in autoantibody-positive RA (mean 1.8 vs 2.4; P = .03) but comparable to that of polyarticular PsA (P = .78). The frequency of lympho-myeloid synovitis was lower in autoantibody-negative RA than in autoantibody-positive RA (38.2% vs 62.9%; P = .07) but comparable to that of polyarticular PsA (P = .8).
Study details: This study included 131 patients who underwent synovial biopsy and were categorized into those having autoantibody-positive RA (n = 43), autoantibody-negative RA (n = 35), symmetric polyarticular PsA (n = 25), and asymmetric oligoarticular PsA (n = 28).
Disclosures: This study was supported by IRCCS Policlinico San Matteo Foundation, Pavia, Italy. C Montecucco and S Bugatti reported receiving grants or research support and personal fees from various sources. The remaining authors declared no conflicts of interest.
Source: De Stefano L et al. Synovial and serum B-cell signature of autoantibody-negative rheumatoid arthritis versus autoantibody-positive rheumatoid arthritis and psoriatic arthritis. Rheumatology (Oxford). 2023 (Jul 22). doi: 10.1093/rheumatology/kead378
Anti-IL-23 treatment may increase the risk for ischemic cerebral stroke in PsA
Key clinical point: Patients with psoriasis or psoriatic arthritis (PsA) treated with anti-interleukin-23 (anti-IL-23) antibodies are at a significantly higher risk for ischemic cerebral stroke (ICS) compared with individuals from the general population.
Major finding: The risk for ICS was significantly higher among patients receiving anti-IL-23 treatment compared with individuals from the general population (hazard ratio 1.770; P = .03).
Study details: This comparative observational study included patients with psoriasis or PsA who received anti-IL-23 (n = 7051), anti-IL-17 (n = 12,215), anti-IL-12/23 (n = 2819), anti-tumor necrosis factor-α (n = 2133), or apremilast (n = 13,139) therapy, whereas individuals with at least 1 healthcare consumption in a month formed the control group (n = 33,428,380).
Disclosures: This study did not receive any funding. T Passeron declared receiving grants or honoraria from various sources. The other authors declared no conflicts of interest.
Source: Bulsei J et al. Ischemic cerebral stroke risk under psoriasis and psoriatic arthritis treatment: A real-world observational study from the French national healthcare system database. J Eur Acad Dermatol Venereol. 2023 (Jul 17). doi: 10.1111/jdv.19356
Key clinical point: Patients with psoriasis or psoriatic arthritis (PsA) treated with anti-interleukin-23 (anti-IL-23) antibodies are at a significantly higher risk for ischemic cerebral stroke (ICS) compared with individuals from the general population.
Major finding: The risk for ICS was significantly higher among patients receiving anti-IL-23 treatment compared with individuals from the general population (hazard ratio 1.770; P = .03).
Study details: This comparative observational study included patients with psoriasis or PsA who received anti-IL-23 (n = 7051), anti-IL-17 (n = 12,215), anti-IL-12/23 (n = 2819), anti-tumor necrosis factor-α (n = 2133), or apremilast (n = 13,139) therapy, whereas individuals with at least 1 healthcare consumption in a month formed the control group (n = 33,428,380).
Disclosures: This study did not receive any funding. T Passeron declared receiving grants or honoraria from various sources. The other authors declared no conflicts of interest.
Source: Bulsei J et al. Ischemic cerebral stroke risk under psoriasis and psoriatic arthritis treatment: A real-world observational study from the French national healthcare system database. J Eur Acad Dermatol Venereol. 2023 (Jul 17). doi: 10.1111/jdv.19356
Key clinical point: Patients with psoriasis or psoriatic arthritis (PsA) treated with anti-interleukin-23 (anti-IL-23) antibodies are at a significantly higher risk for ischemic cerebral stroke (ICS) compared with individuals from the general population.
Major finding: The risk for ICS was significantly higher among patients receiving anti-IL-23 treatment compared with individuals from the general population (hazard ratio 1.770; P = .03).
Study details: This comparative observational study included patients with psoriasis or PsA who received anti-IL-23 (n = 7051), anti-IL-17 (n = 12,215), anti-IL-12/23 (n = 2819), anti-tumor necrosis factor-α (n = 2133), or apremilast (n = 13,139) therapy, whereas individuals with at least 1 healthcare consumption in a month formed the control group (n = 33,428,380).
Disclosures: This study did not receive any funding. T Passeron declared receiving grants or honoraria from various sources. The other authors declared no conflicts of interest.
Source: Bulsei J et al. Ischemic cerebral stroke risk under psoriasis and psoriatic arthritis treatment: A real-world observational study from the French national healthcare system database. J Eur Acad Dermatol Venereol. 2023 (Jul 17). doi: 10.1111/jdv.19356
Ultrasound can be a useful tool in detecting subclinical juvenile psoriatic arthritis
Key clinical point: Musculoskeletal ultrasound along with physical examination can help identify juvenile psoriatic arthritis in pediatric patients with skin psoriasis showing musculoskeletal symptoms.
Major finding: Ultrasound evaluation showed higher number of joint and enthesitis abnormalities in pediatric patients with psoriasis who were symptomatic vs asymptomatic for musculoskeletal pain or swelling (all P ≤ .01). The concordance for detecting synovitis and enthesitis between physical and ultrasound examination was 82%.
Study details: Findings are from a cross-sectional study including 57 pediatric patients with psoriasis and no previous diagnosis of juvenile idiopathic arthritis or any systemic disease-causing articular manifestations who underwent ultrasound evaluation and clinical examination.
Disclosures: This study was supported by the PARTNER Fellowship program created with an unrestricted grant by Celgene-AMGEN, with L Coronel as a PARTNER fellow. Two authors declared ties with various sources, including Amgen. Two authors declared no conflicts of interest.
Source: Coronel L et al. Prevalence of ultrasound and clinical findings suggestive of inflammatory arthritis in children with skin psoriasis. Rheumatology (Oxford). 2023 (Aug 4). doi: 10.1093/rheumatology/kead398
Key clinical point: Musculoskeletal ultrasound along with physical examination can help identify juvenile psoriatic arthritis in pediatric patients with skin psoriasis showing musculoskeletal symptoms.
Major finding: Ultrasound evaluation showed higher number of joint and enthesitis abnormalities in pediatric patients with psoriasis who were symptomatic vs asymptomatic for musculoskeletal pain or swelling (all P ≤ .01). The concordance for detecting synovitis and enthesitis between physical and ultrasound examination was 82%.
Study details: Findings are from a cross-sectional study including 57 pediatric patients with psoriasis and no previous diagnosis of juvenile idiopathic arthritis or any systemic disease-causing articular manifestations who underwent ultrasound evaluation and clinical examination.
Disclosures: This study was supported by the PARTNER Fellowship program created with an unrestricted grant by Celgene-AMGEN, with L Coronel as a PARTNER fellow. Two authors declared ties with various sources, including Amgen. Two authors declared no conflicts of interest.
Source: Coronel L et al. Prevalence of ultrasound and clinical findings suggestive of inflammatory arthritis in children with skin psoriasis. Rheumatology (Oxford). 2023 (Aug 4). doi: 10.1093/rheumatology/kead398
Key clinical point: Musculoskeletal ultrasound along with physical examination can help identify juvenile psoriatic arthritis in pediatric patients with skin psoriasis showing musculoskeletal symptoms.
Major finding: Ultrasound evaluation showed higher number of joint and enthesitis abnormalities in pediatric patients with psoriasis who were symptomatic vs asymptomatic for musculoskeletal pain or swelling (all P ≤ .01). The concordance for detecting synovitis and enthesitis between physical and ultrasound examination was 82%.
Study details: Findings are from a cross-sectional study including 57 pediatric patients with psoriasis and no previous diagnosis of juvenile idiopathic arthritis or any systemic disease-causing articular manifestations who underwent ultrasound evaluation and clinical examination.
Disclosures: This study was supported by the PARTNER Fellowship program created with an unrestricted grant by Celgene-AMGEN, with L Coronel as a PARTNER fellow. Two authors declared ties with various sources, including Amgen. Two authors declared no conflicts of interest.
Source: Coronel L et al. Prevalence of ultrasound and clinical findings suggestive of inflammatory arthritis in children with skin psoriasis. Rheumatology (Oxford). 2023 (Aug 4). doi: 10.1093/rheumatology/kead398
Factors associated with depressive symptoms in PsA
Key clinical point: Depression is prevalent in patients with psoriatic arthritis (PsA), with patients not engaging in sports activities, experiencing fatigue, and having functional impairment being more likely to suffer from depression.
Major finding: Overall, 8.2% and 20.9% of patients with PsA had severe and moderate depressive symptoms, respectively. The odds of having depressive symptoms were higher in patients with functional impairment (odds ratio [OR] 1.08; P < .0001) and those experiencing fatigue (OR 1.56; P < .0001), whereas those engaging in sports for at least 1 hour/week were less likely to be depressed (OR 0.61; P = .0017).
Study details: This study included 1225 patients with PsA and 1245 patients with axial spondyloarthritis from the RABBIT-SpA cohort.
Disclosures: This study received open access funding from Projekt Deal, and RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biogen, and various other sources. The authors declared no conflicts of interest.
Source: Reich A et al. Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: An analysis from the RABBIT-SpA cohort. Arthritis Res Ther. 2023;25:136 (Aug 2). doi: 10.1186/s13075-023-03127-2.
Key clinical point: Depression is prevalent in patients with psoriatic arthritis (PsA), with patients not engaging in sports activities, experiencing fatigue, and having functional impairment being more likely to suffer from depression.
Major finding: Overall, 8.2% and 20.9% of patients with PsA had severe and moderate depressive symptoms, respectively. The odds of having depressive symptoms were higher in patients with functional impairment (odds ratio [OR] 1.08; P < .0001) and those experiencing fatigue (OR 1.56; P < .0001), whereas those engaging in sports for at least 1 hour/week were less likely to be depressed (OR 0.61; P = .0017).
Study details: This study included 1225 patients with PsA and 1245 patients with axial spondyloarthritis from the RABBIT-SpA cohort.
Disclosures: This study received open access funding from Projekt Deal, and RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biogen, and various other sources. The authors declared no conflicts of interest.
Source: Reich A et al. Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: An analysis from the RABBIT-SpA cohort. Arthritis Res Ther. 2023;25:136 (Aug 2). doi: 10.1186/s13075-023-03127-2.
Key clinical point: Depression is prevalent in patients with psoriatic arthritis (PsA), with patients not engaging in sports activities, experiencing fatigue, and having functional impairment being more likely to suffer from depression.
Major finding: Overall, 8.2% and 20.9% of patients with PsA had severe and moderate depressive symptoms, respectively. The odds of having depressive symptoms were higher in patients with functional impairment (odds ratio [OR] 1.08; P < .0001) and those experiencing fatigue (OR 1.56; P < .0001), whereas those engaging in sports for at least 1 hour/week were less likely to be depressed (OR 0.61; P = .0017).
Study details: This study included 1225 patients with PsA and 1245 patients with axial spondyloarthritis from the RABBIT-SpA cohort.
Disclosures: This study received open access funding from Projekt Deal, and RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biogen, and various other sources. The authors declared no conflicts of interest.
Source: Reich A et al. Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: An analysis from the RABBIT-SpA cohort. Arthritis Res Ther. 2023;25:136 (Aug 2). doi: 10.1186/s13075-023-03127-2.