MDedge Endocrinology

It is well established that LGBTQ individuals experience more health disparities compared with their cisgender, heterosexual counterparts. In general, LGBTQ adolescents and young adults have higher levels of depression, suicide attempts, and substance use than those of their heterosexual peers. However, a key protective factor is family acceptance and support. By encouraging families to modify and change behaviors that are experienced by their LGBTQ children as rejecting and to engage in supportive and affirming behaviors, providers can help families to decrease risk and promote healthy outcomes for LGBTQ youth and young adults.

The Family Acceptance Project

The Family Acceptance Project

The Family Acceptance Project

To reduce risk, pediatricians should ask LGBTQ patients about family rejecting behaviors and help parents and caregivers to identify and understand the effect of such behaviors to reduce health risks and conflict that can lead to running away, expulsion, and removal from the home. Even decreasing rejecting behaviors to moderate levels can significantly improve negative outcomes.⁵

Caitlin Ryan, PhD, and her team also identified and measured more than 50 family accepting behaviors that help protect against risk and promote well-being. They found that young adults who experience high levels of family acceptance during adolescence report significantly higher levels of self-esteem, social support, and general health with much lower levels of depression, suicidality, and substance abuse.⁷ Family accepting and supportive behaviors include talking with the child about their LGBTQ identity; advocating for their LGBTQ child when others mistreat them; requiring other family members to treat their LGBTQ child with respect; and supporting their child’s gender identity.⁵ FAP has developed an evidence-informed family support model and multilingual educational resources for families, providers, youth and religious leaders to decrease rejection and increase family support. These are available in print copies and for download at familyproject.sfsu.edu.

In addition, Dr. Ryan and colleagues^1,4,8 recommend the following guidance for providers:

• Ask LGBTQ adolescents about family reactions to their sexual orientation, gender identity, and expression, and refer to LGBTQ community support programs and for supportive counseling, as needed.
• Identify LGBTQ community support programs and online resources to educate parents about how to help their children. Parents need culturally relevant peer support to help decrease rejection and increase family support.
• Advise parents that negative reactions to their adolescent’s LGBTQ identity may negatively impact their child’s health and mental health while supportive and affirming reactions promote well-being.
• Advise parents and caregivers to modify and change family rejecting behaviors that increase their child’s risk for suicide, depression, substance abuse ,and risky sexual behaviors.
• Expand anticipatory guidance to include information on the need for support and the link between family rejection and negative health problems.
• Provide guidance on sexual orientation and gender identity as part of normative child development during well-baby and early childhood care.
• Use FAP’s multilingual family education booklets and Healthy Futures poster series in family and patient education and provide these materials in clinical and community settings. FAP’s Healthy Futures posters include a poster guidance, a version on family acceptance, a version on family rejection and a family acceptance version for conservative families and settings. They are available in camera-ready art in four sizes in English and Spanish and are forthcoming in five Asian languages: familyproject.sfsu.edu/poster.

Dr. Lawlis is assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, and an adolescent medicine specialist at OU Children’s. She has no relevant financial disclosures.
 

Resources

• Family Acceptance Project – consultation and training; evidence-based educational materials for families, providers, religious leaders and youth.

• PFLAG – peer support for parents and friends with LGBTQ children in all states and several other countries.
 

References

1. Ryan C. Generating a revolution in prevention, wellness & care for LGBT children & youth. Temple Political & Civil Rights Law Review. 2014;23(2):331-44.

2. Ryan C. Healthy Futures Poster Series – Family Accepting & Rejecting Behaviors That Impact LGBTQ Children’s Health & Well-Being. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2019.

3. Ryan C. Family Acceptance Project: Culturally grounded framework for supporting LGBTQ children and youth. J Am Acad Child Adolesc Psychiatr. 2019;58(10):S58-9.

4. Ryan C et al. Family rejection as a predictor of negative health outcomes in White and Latino lesbian, gay, and bisexual young adults. Pediatrics. 2009;123(1):346-52.

5. Ryan C. Supportive families, healthy children: Helping families with lesbian, gay, bisexual & transgender children. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2009.

6. Ryan C et al. Parent-initiated sexual orientation change efforts with LGBT adolescents: Implications for young adult mental health and adjustment. J Homosexuality. 2020;67(2):159-73.

7. Ryan C et al. Family acceptance in adolescence and the health of LGBT young adults. J Child Adolesc Psychiatr Nursing. 2010;23(4):205-13. 8. Substance Abuse and Mental Health Services Administration. A Practitioner’s Guide: Helping Families to Support Their LGBT Children. In: Administration SAaMhS, ed. Vol PEP14-LGBTKIDS. Rockville, MD: HHS Publication; 2014.

It is well established that LGBTQ individuals experience more health disparities compared with their cisgender, heterosexual counterparts. In general, LGBTQ adolescents and young adults have higher levels of depression, suicide attempts, and substance use than those of their heterosexual peers. However, a key protective factor is family acceptance and support. By encouraging families to modify and change behaviors that are experienced by their LGBTQ children as rejecting and to engage in supportive and affirming behaviors, providers can help families to decrease risk and promote healthy outcomes for LGBTQ youth and young adults.

The Family Acceptance Project

The Family Acceptance Project

The Family Acceptance Project

To reduce risk, pediatricians should ask LGBTQ patients about family rejecting behaviors and help parents and caregivers to identify and understand the effect of such behaviors to reduce health risks and conflict that can lead to running away, expulsion, and removal from the home. Even decreasing rejecting behaviors to moderate levels can significantly improve negative outcomes.⁵

Caitlin Ryan, PhD, and her team also identified and measured more than 50 family accepting behaviors that help protect against risk and promote well-being. They found that young adults who experience high levels of family acceptance during adolescence report significantly higher levels of self-esteem, social support, and general health with much lower levels of depression, suicidality, and substance abuse.⁷ Family accepting and supportive behaviors include talking with the child about their LGBTQ identity; advocating for their LGBTQ child when others mistreat them; requiring other family members to treat their LGBTQ child with respect; and supporting their child’s gender identity.⁵ FAP has developed an evidence-informed family support model and multilingual educational resources for families, providers, youth and religious leaders to decrease rejection and increase family support. These are available in print copies and for download at familyproject.sfsu.edu.

In addition, Dr. Ryan and colleagues^1,4,8 recommend the following guidance for providers:

• Ask LGBTQ adolescents about family reactions to their sexual orientation, gender identity, and expression, and refer to LGBTQ community support programs and for supportive counseling, as needed.
• Identify LGBTQ community support programs and online resources to educate parents about how to help their children. Parents need culturally relevant peer support to help decrease rejection and increase family support.
• Advise parents that negative reactions to their adolescent’s LGBTQ identity may negatively impact their child’s health and mental health while supportive and affirming reactions promote well-being.
• Advise parents and caregivers to modify and change family rejecting behaviors that increase their child’s risk for suicide, depression, substance abuse ,and risky sexual behaviors.
• Expand anticipatory guidance to include information on the need for support and the link between family rejection and negative health problems.
• Provide guidance on sexual orientation and gender identity as part of normative child development during well-baby and early childhood care.
• Use FAP’s multilingual family education booklets and Healthy Futures poster series in family and patient education and provide these materials in clinical and community settings. FAP’s Healthy Futures posters include a poster guidance, a version on family acceptance, a version on family rejection and a family acceptance version for conservative families and settings. They are available in camera-ready art in four sizes in English and Spanish and are forthcoming in five Asian languages: familyproject.sfsu.edu/poster.

Dr. Lawlis is assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, and an adolescent medicine specialist at OU Children’s. She has no relevant financial disclosures.
 

Resources

• Family Acceptance Project – consultation and training; evidence-based educational materials for families, providers, religious leaders and youth.

• PFLAG – peer support for parents and friends with LGBTQ children in all states and several other countries.
 

References

1. Ryan C. Generating a revolution in prevention, wellness & care for LGBT children & youth. Temple Political & Civil Rights Law Review. 2014;23(2):331-44.

2. Ryan C. Healthy Futures Poster Series – Family Accepting & Rejecting Behaviors That Impact LGBTQ Children’s Health & Well-Being. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2019.

3. Ryan C. Family Acceptance Project: Culturally grounded framework for supporting LGBTQ children and youth. J Am Acad Child Adolesc Psychiatr. 2019;58(10):S58-9.

4. Ryan C et al. Family rejection as a predictor of negative health outcomes in White and Latino lesbian, gay, and bisexual young adults. Pediatrics. 2009;123(1):346-52.

5. Ryan C. Supportive families, healthy children: Helping families with lesbian, gay, bisexual & transgender children. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2009.

6. Ryan C et al. Parent-initiated sexual orientation change efforts with LGBT adolescents: Implications for young adult mental health and adjustment. J Homosexuality. 2020;67(2):159-73.

7. Ryan C et al. Family acceptance in adolescence and the health of LGBT young adults. J Child Adolesc Psychiatr Nursing. 2010;23(4):205-13. 8. Substance Abuse and Mental Health Services Administration. A Practitioner’s Guide: Helping Families to Support Their LGBT Children. In: Administration SAaMhS, ed. Vol PEP14-LGBTKIDS. Rockville, MD: HHS Publication; 2014.

It is well established that LGBTQ individuals experience more health disparities compared with their cisgender, heterosexual counterparts. In general, LGBTQ adolescents and young adults have higher levels of depression, suicide attempts, and substance use than those of their heterosexual peers. However, a key protective factor is family acceptance and support. By encouraging families to modify and change behaviors that are experienced by their LGBTQ children as rejecting and to engage in supportive and affirming behaviors, providers can help families to decrease risk and promote healthy outcomes for LGBTQ youth and young adults.

The Family Acceptance Project

The Family Acceptance Project

The Family Acceptance Project

To reduce risk, pediatricians should ask LGBTQ patients about family rejecting behaviors and help parents and caregivers to identify and understand the effect of such behaviors to reduce health risks and conflict that can lead to running away, expulsion, and removal from the home. Even decreasing rejecting behaviors to moderate levels can significantly improve negative outcomes.⁵

Caitlin Ryan, PhD, and her team also identified and measured more than 50 family accepting behaviors that help protect against risk and promote well-being. They found that young adults who experience high levels of family acceptance during adolescence report significantly higher levels of self-esteem, social support, and general health with much lower levels of depression, suicidality, and substance abuse.⁷ Family accepting and supportive behaviors include talking with the child about their LGBTQ identity; advocating for their LGBTQ child when others mistreat them; requiring other family members to treat their LGBTQ child with respect; and supporting their child’s gender identity.⁵ FAP has developed an evidence-informed family support model and multilingual educational resources for families, providers, youth and religious leaders to decrease rejection and increase family support. These are available in print copies and for download at familyproject.sfsu.edu.

In addition, Dr. Ryan and colleagues^1,4,8 recommend the following guidance for providers:

• Ask LGBTQ adolescents about family reactions to their sexual orientation, gender identity, and expression, and refer to LGBTQ community support programs and for supportive counseling, as needed.
• Identify LGBTQ community support programs and online resources to educate parents about how to help their children. Parents need culturally relevant peer support to help decrease rejection and increase family support.
• Advise parents that negative reactions to their adolescent’s LGBTQ identity may negatively impact their child’s health and mental health while supportive and affirming reactions promote well-being.
• Advise parents and caregivers to modify and change family rejecting behaviors that increase their child’s risk for suicide, depression, substance abuse ,and risky sexual behaviors.
• Expand anticipatory guidance to include information on the need for support and the link between family rejection and negative health problems.
• Provide guidance on sexual orientation and gender identity as part of normative child development during well-baby and early childhood care.
• Use FAP’s multilingual family education booklets and Healthy Futures poster series in family and patient education and provide these materials in clinical and community settings. FAP’s Healthy Futures posters include a poster guidance, a version on family acceptance, a version on family rejection and a family acceptance version for conservative families and settings. They are available in camera-ready art in four sizes in English and Spanish and are forthcoming in five Asian languages: familyproject.sfsu.edu/poster.

Dr. Lawlis is assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, and an adolescent medicine specialist at OU Children’s. She has no relevant financial disclosures.
 

Resources

• Family Acceptance Project – consultation and training; evidence-based educational materials for families, providers, religious leaders and youth.

• PFLAG – peer support for parents and friends with LGBTQ children in all states and several other countries.
 

References

1. Ryan C. Generating a revolution in prevention, wellness & care for LGBT children & youth. Temple Political & Civil Rights Law Review. 2014;23(2):331-44.

2. Ryan C. Healthy Futures Poster Series – Family Accepting & Rejecting Behaviors That Impact LGBTQ Children’s Health & Well-Being. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2019.

3. Ryan C. Family Acceptance Project: Culturally grounded framework for supporting LGBTQ children and youth. J Am Acad Child Adolesc Psychiatr. 2019;58(10):S58-9.

4. Ryan C et al. Family rejection as a predictor of negative health outcomes in White and Latino lesbian, gay, and bisexual young adults. Pediatrics. 2009;123(1):346-52.

5. Ryan C. Supportive families, healthy children: Helping families with lesbian, gay, bisexual & transgender children. In: Family Acceptance Project Marian Wright Edelman Institute SFSU, ed. San Francisco, CA2009.

6. Ryan C et al. Parent-initiated sexual orientation change efforts with LGBT adolescents: Implications for young adult mental health and adjustment. J Homosexuality. 2020;67(2):159-73.

7. Ryan C et al. Family acceptance in adolescence and the health of LGBT young adults. J Child Adolesc Psychiatr Nursing. 2010;23(4):205-13. 8. Substance Abuse and Mental Health Services Administration. A Practitioner’s Guide: Helping Families to Support Their LGBT Children. In: Administration SAaMhS, ed. Vol PEP14-LGBTKIDS. Rockville, MD: HHS Publication; 2014.

In support of previously published case reports, a study using cross-linked national population data in Denmark has now associated cumulative exposure to high-potency topical steroids with osteoporotic fractures in a dose-response relationship.

In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.

“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.

The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.

Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.

For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.

The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.

“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.

Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.

“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”

If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.

The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.

The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.

“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said

For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.

“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.

In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”

The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.

“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.

To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.

Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.

In support of previously published case reports, a study using cross-linked national population data in Denmark has now associated cumulative exposure to high-potency topical steroids with osteoporotic fractures in a dose-response relationship.

In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.

“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.

The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.

Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.

For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.

The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.

“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.

Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.

“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”

If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.

The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.

The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.

“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said

For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.

“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.

In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”

The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.

“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.

To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.

Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.

In support of previously published case reports, a study using cross-linked national population data in Denmark has now associated cumulative exposure to high-potency topical steroids with osteoporotic fractures in a dose-response relationship.

In a stepwise manner, the hazard ratios for major osteoporotic fracture (MOF) were found to start climbing incrementally for those with a cumulative topical steroid dose equivalent of more than 500 g of mometasone furoate when compared with exposure of 200-499 g, according to the team of investigators from the University of Copenhagen.

“Use of these drugs is very common, and we found an estimated population-attributable risk of as much as 4.3%,” the investigators reported in the study, published in JAMA Dermatology.

The retrospective cohort study drew data from the Danish National Patient Registry, which covers 99% of the country’s population. It was linked to the Danish National Prescription Registry, which captures data on pharmacy-dispensed medications. Data collected from the beginning of 2003 to the end of 2017 were evaluated.

Exposures to potent or very potent topical corticosteroids were converted into a single standard with potency equivalent to 1 mg/g of mometasone furoate. Four strata of exposure were compared to a reference exposure of 200-499 g. These were 500-999 g, 1,000-1,999 g, 2,000-9,999 g, and 10,000 g or greater.

For the first strata, the small increased risk for MOF did not reach significance (HR, 1.01; 95% confidence interval, 0.99-1.03), but each of the others did. These climbed from a 5% greater risk (HR 1.05 95% CI 1.02-1.08) for a cumulative exposure of 1,000 to 1,999 g, to a 10% greater risk (HR, 1.10; 95% CI, 1.07-1.13) for a cumulative exposure of 2,000-9,999 g, and finally to a 27% greater risk (HR, 1.27; 95% CI, 1.19-1.35) for a cumulative exposure of 10,000 g or higher.

The study included more than 700,000 individuals exposed to topical mometasone at a potency equivalent of 200 g or more over the study period. The reference group (200-499 g) was the largest (317,907 individuals). The first strata (500-999 g) included 186,359 patients; the second (1,000-1,999 g), 111,203 patients; the third (2,000-9,999 g), 94,334 patients; and the fifth (10,000 g or more), 13,448 patients.

“A 3% increase in the relative risk of osteoporosis and MOF was observed per doubling of the TCS dose,” according to the investigators.

Patients exposed to doses of high-potency topical steroids that put them at risk of MOF is limited but substantial, according to the senior author, Alexander Egeberg, MD, PhD, of the department of dermatology and allergy at Herlev and Gentofte Hospital, Copenhagen.

“It is true that the risk is modest for the average user of topical steroids,” Dr. Egeberg said in an interview. However, despite the fact that topical steroids are intended for short-term use, “2% of all our users had been exposed to the equivalent of 10,000 g of mometasone, which mean 100 tubes of 100 g.”

If the other two strata at significantly increased risk of MOF (greater than 1,000 g) are included, an additional 28% of all users are facing the potential for clinically significant osteoporosis, according to the Danish data.

The adverse effect of steroids on bone metabolism has been established previously, and several studies have linked systemic corticosteroid exposure, including inhaled corticosteroids, with increased risk of osteoporotic fracture. For example, one study showed that patients with chronic obstructive pulmonary disease on daily inhaled doses of the equivalent of fluticasone at or above 1,000 mcg for more than 4 years had about a 10% increased risk of MOF relative to those not exposed.

The data associate topical steroids with increased risk of osteoporotic fracture, but Dr. Egeberg said osteoporosis is not the only reason to use topical steroids prudently.

“It is important to keep in mind that osteoporosis and fractures are at the extreme end of the side-effect profile and that other side effects, such as striae formation, skin thinning, and dysregulated diabetes, can occur with much lower quantities of topical steroids,” Dr. Egeberg said

For avoiding this risk, “there are no specific cutoffs” recommended for topical steroids in current guidelines, but dermatologists should be aware that many of the indications for topical steroids, such as psoriasis and atopic dermatitis, involve skin with an impaired barrier function, exposing patients to an increased likelihood of absorption, according to Dr. Egeberg.

“A general rule of thumb that we use is that, if a patient with persistent disease activity requires a new prescription of the equivalent of 100 g mometasone every 1-2 months, it might be worth considering if there is a suitable alternative,” Dr. Egeberg said.

In an accompanying editorial, Rebecca D. Jackson, MD, of the division of endocrinology, diabetes, and metabolism in the department of internal medicine at Ohio State University, Columbus, agreed that no guidelines specific to avoiding the risks of topical corticosteroids are currently available, but she advised clinicians to be considering these risks nonetheless. In general, she suggested that topical steroids, like oral steroids, should be used at “the lowest dose for the shortest duration necessary to manage the underlying medical condition.”

The correlation between topical corticosteroids and increased risk of osteoporotic fracture, although not established previously in a large study, is not surprising, according to Victoria Werth, MD, chief of dermatology at the Philadelphia Veterans Affairs Hospital and professor of dermatology at the University of Pennsylvania, also in Philadelphia.

“Systemic absorption of potent topical steroids has previously been demonstrated with a rapid decrease in serum cortisol levels,” Dr. Werth said in an interview. She indicated that concern about the risk of osteoporosis imposed by use of potent steroids over large body surface areas is appropriate.

To minimize this risk, “it is reasonable to use the lowest dose of steroid possible and to try to substitute other medications when possible,” she said.

Dr. Egeberg reported financial relationships with Abbvie, Almirall, Bristol-Myers Squibb, Dermavant Sciences, Galderma, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Samsung, Bioepis, and UCB. Five authors had disclosures related to some of those pharmaceutical companies and/or others. Dr. Jackson had no disclosures.

A commercial for the continuous glucose monitor (CGM) Dexcom G6 shown during the Super Bowl has provoked strong reactions in the diabetes community, both positive and negative.

The 30-second ad, which aired between the first two quarters of the American football game yesterday, features singer-songwriter-actor Nick Jonas, who has type 1 diabetes. During the ad, Mr. Jonas asks – with so much technology available today, including drones that deliver packages and self-driving cars – why are people with diabetes still pricking their fingers to test their blood sugar?

Mr. Jonas goes on to demonstrate the Dexcom G6 smartphone glucose app as it displays three different glucose levels including two trending upward, explaining: “It shows your glucose right in your phone, and where it’s heading, without fingersticks. Finally, technology that makes it easier to manage our diabetes.”

Diabetes type or insulin treatment are not mentioned in the ad, despite the fact that most insurance plans typically only cover CGMs for people with type 1 diabetes and sometimes for those with type 2 diabetes who take multiple daily insulin doses (given the risk for hypoglycemia).
 

Ad prompts mixed reaction on social media

Reactions rolled in on Twitter after the ad debuted Feb. 2, and then again after it aired during the game.

Some people who have type 1 diabetes themselves or have children with the disease who use the product were thrilled.

“Thanks to @NickJonas for his advocacy on T1. My 11-year old has been on the Dexcom for 3 weeks. For a newly diagnosed kid, it removes a lot of anxiety (and for his parents, too!) Plus, he is thrilled his meter has a Super Bowl commercial!” tweeted @KatisJewell.

Another positive tweet, from @rturnerroy, read: “@nickjonas Thank you for bringing representation to #type1diabetes. And hey #Dexcom, you’re the best.”

But many others were critical, both of Jonas and Dexcom. @hb_herrick tweeted: “Diabetes awareness is fantastic. Dexcom being able to afford Nick Jonas for a #SuperBowl commercial is not. This is a health care product. Make it more affordable for those who need it.”

Another Twitter user, @universeofdust, tweeted: “Feeling ambivalent about the #Dexcom ad tbh. I love the awareness & representation. But also not a big fan of dexcom spending $5.5 mill+ to make the CGM seem like this ~cool & trendy~ thing when many type 1s can’t afford their insulin, let alone a CGM.”

And @andricheli wrote: “Only people lucky enough to have excellent insurance and be able to afford the out-of-pocket costs have access. Many others do not.”

And in another tweet the same user said, “The #Dexcom is an amazing device. It’s literally lifesaving and life extending. But it’s also very expensive and not available to everyone. Maybe instead of spending $5 mil on a Super Bowl ad, @dexcom should spend that on getting Dex into the handle of people who need it.”

Others, including @1hitwonderdate, criticized Mr. Jonas directly, asking him: “As someone who has struggled with diabetes and is trying to support themselves along with millions of others, why not use this platform to help those who can’t afford their supplies or are rationing them?!”


 

Dexcom and Jonas’ organization respond

This news organization reached out to both Dexcom and to Beyond Type 1, a nonprofit organization cofounded by Mr. Jonas, for comment. Both emailed responses.

Regarding the intended audience for the ad, Dexcom acknowledged that it hoped to reach a much wider group than just people with type 1 diabetes or even just insulin users.

“We believe our CGM technology has the ability to empower any person with diabetes and significantly improve their treatment and quality of life, whether they are using insulin or not,” the company said, adding that the ad was also aimed at “loved ones, caregivers, and even health care professionals who need to know about this technology.”

According to Dexcom, the G6 is covered by 99% of commercial insurance in the United States, in addition to Medicare, and by Medicaid in more than 40 states. Over 70% of Dexcom patients with pharmacy coverage in the United States pay under $60 per month for CGM, and a third pay $0 out-of-pocket.

“That said, we know there’s more to be done to improve access, and we are working with several partners to broaden access to Dexcom CGM, especially for people with type 2 diabetes not on mealtime insulin,” the company noted.

Beyond Type 1 responded to the criticisms about Mr. Jonas personally, noting that the celebrity is, in fact, heavily involved in advocacy.

“Nick was involved in the launch of GetInsulin.org this past October,” they said. “GetInsulin.org is a tool created by Beyond Type 1 to connect people with diabetes in the United States to the insulin access and affordability options that match their unique circumstances. ... Beyond Type 1 will continue driving awareness of short-term solutions related to insulin access and affordability while fighting for systemic change.”

The organization “is also advocating for systemic payment policies that will make devices less expensive and avoid the same pitfalls (and rising prices) as the drug pricing system in the U.S.”

Mr. Jonas himself appears aware of the concerns.

Is 2021’s most expensive Super Bowl ad justified?

Meanwhile, in a piece in Esquire, Dave Holmes, who has type 1 diabetes, weighs up the pros and cons of the ad.

He writes: “While Jonas makes it look fun and easy to use a Dexcom G6 – a program to just get with like you would a drone or LED eyelashes – the process of acquiring one is complicated and often very expensive, even for people with good insurance. Which makes the year’s most expensive ad buy, for a product that only a small percentage of the U.S. population needs, confusing to me and others.”

Mr. Holmes also spoke with Craig Stubing, founder of the Beta Cell Foundation, a nonprofit that aims to educate and empower those with type 1 diabetes.

“Spending all this money on an ad, when people’s lives are at stake. I don’t know if offensive is the right word, but it seems out of touch with the reality that their patients are facing,” Mr. Stubing told Mr. Holmes.

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

A commercial for the continuous glucose monitor (CGM) Dexcom G6 shown during the Super Bowl has provoked strong reactions in the diabetes community, both positive and negative.

The 30-second ad, which aired between the first two quarters of the American football game yesterday, features singer-songwriter-actor Nick Jonas, who has type 1 diabetes. During the ad, Mr. Jonas asks – with so much technology available today, including drones that deliver packages and self-driving cars – why are people with diabetes still pricking their fingers to test their blood sugar?

Mr. Jonas goes on to demonstrate the Dexcom G6 smartphone glucose app as it displays three different glucose levels including two trending upward, explaining: “It shows your glucose right in your phone, and where it’s heading, without fingersticks. Finally, technology that makes it easier to manage our diabetes.”

Diabetes type or insulin treatment are not mentioned in the ad, despite the fact that most insurance plans typically only cover CGMs for people with type 1 diabetes and sometimes for those with type 2 diabetes who take multiple daily insulin doses (given the risk for hypoglycemia).
 

Ad prompts mixed reaction on social media

Reactions rolled in on Twitter after the ad debuted Feb. 2, and then again after it aired during the game.

Some people who have type 1 diabetes themselves or have children with the disease who use the product were thrilled.

“Thanks to @NickJonas for his advocacy on T1. My 11-year old has been on the Dexcom for 3 weeks. For a newly diagnosed kid, it removes a lot of anxiety (and for his parents, too!) Plus, he is thrilled his meter has a Super Bowl commercial!” tweeted @KatisJewell.

Another positive tweet, from @rturnerroy, read: “@nickjonas Thank you for bringing representation to #type1diabetes. And hey #Dexcom, you’re the best.”

But many others were critical, both of Jonas and Dexcom. @hb_herrick tweeted: “Diabetes awareness is fantastic. Dexcom being able to afford Nick Jonas for a #SuperBowl commercial is not. This is a health care product. Make it more affordable for those who need it.”

Another Twitter user, @universeofdust, tweeted: “Feeling ambivalent about the #Dexcom ad tbh. I love the awareness & representation. But also not a big fan of dexcom spending $5.5 mill+ to make the CGM seem like this ~cool & trendy~ thing when many type 1s can’t afford their insulin, let alone a CGM.”

And @andricheli wrote: “Only people lucky enough to have excellent insurance and be able to afford the out-of-pocket costs have access. Many others do not.”

And in another tweet the same user said, “The #Dexcom is an amazing device. It’s literally lifesaving and life extending. But it’s also very expensive and not available to everyone. Maybe instead of spending $5 mil on a Super Bowl ad, @dexcom should spend that on getting Dex into the handle of people who need it.”

Others, including @1hitwonderdate, criticized Mr. Jonas directly, asking him: “As someone who has struggled with diabetes and is trying to support themselves along with millions of others, why not use this platform to help those who can’t afford their supplies or are rationing them?!”


 

Dexcom and Jonas’ organization respond

This news organization reached out to both Dexcom and to Beyond Type 1, a nonprofit organization cofounded by Mr. Jonas, for comment. Both emailed responses.

Regarding the intended audience for the ad, Dexcom acknowledged that it hoped to reach a much wider group than just people with type 1 diabetes or even just insulin users.

“We believe our CGM technology has the ability to empower any person with diabetes and significantly improve their treatment and quality of life, whether they are using insulin or not,” the company said, adding that the ad was also aimed at “loved ones, caregivers, and even health care professionals who need to know about this technology.”

According to Dexcom, the G6 is covered by 99% of commercial insurance in the United States, in addition to Medicare, and by Medicaid in more than 40 states. Over 70% of Dexcom patients with pharmacy coverage in the United States pay under $60 per month for CGM, and a third pay $0 out-of-pocket.

“That said, we know there’s more to be done to improve access, and we are working with several partners to broaden access to Dexcom CGM, especially for people with type 2 diabetes not on mealtime insulin,” the company noted.

Beyond Type 1 responded to the criticisms about Mr. Jonas personally, noting that the celebrity is, in fact, heavily involved in advocacy.

“Nick was involved in the launch of GetInsulin.org this past October,” they said. “GetInsulin.org is a tool created by Beyond Type 1 to connect people with diabetes in the United States to the insulin access and affordability options that match their unique circumstances. ... Beyond Type 1 will continue driving awareness of short-term solutions related to insulin access and affordability while fighting for systemic change.”

The organization “is also advocating for systemic payment policies that will make devices less expensive and avoid the same pitfalls (and rising prices) as the drug pricing system in the U.S.”

Mr. Jonas himself appears aware of the concerns.

Is 2021’s most expensive Super Bowl ad justified?

Meanwhile, in a piece in Esquire, Dave Holmes, who has type 1 diabetes, weighs up the pros and cons of the ad.

He writes: “While Jonas makes it look fun and easy to use a Dexcom G6 – a program to just get with like you would a drone or LED eyelashes – the process of acquiring one is complicated and often very expensive, even for people with good insurance. Which makes the year’s most expensive ad buy, for a product that only a small percentage of the U.S. population needs, confusing to me and others.”

Mr. Holmes also spoke with Craig Stubing, founder of the Beta Cell Foundation, a nonprofit that aims to educate and empower those with type 1 diabetes.

“Spending all this money on an ad, when people’s lives are at stake. I don’t know if offensive is the right word, but it seems out of touch with the reality that their patients are facing,” Mr. Stubing told Mr. Holmes.

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

A commercial for the continuous glucose monitor (CGM) Dexcom G6 shown during the Super Bowl has provoked strong reactions in the diabetes community, both positive and negative.

The 30-second ad, which aired between the first two quarters of the American football game yesterday, features singer-songwriter-actor Nick Jonas, who has type 1 diabetes. During the ad, Mr. Jonas asks – with so much technology available today, including drones that deliver packages and self-driving cars – why are people with diabetes still pricking their fingers to test their blood sugar?

Mr. Jonas goes on to demonstrate the Dexcom G6 smartphone glucose app as it displays three different glucose levels including two trending upward, explaining: “It shows your glucose right in your phone, and where it’s heading, without fingersticks. Finally, technology that makes it easier to manage our diabetes.”

Diabetes type or insulin treatment are not mentioned in the ad, despite the fact that most insurance plans typically only cover CGMs for people with type 1 diabetes and sometimes for those with type 2 diabetes who take multiple daily insulin doses (given the risk for hypoglycemia).
 

Ad prompts mixed reaction on social media

Reactions rolled in on Twitter after the ad debuted Feb. 2, and then again after it aired during the game.

Some people who have type 1 diabetes themselves or have children with the disease who use the product were thrilled.

“Thanks to @NickJonas for his advocacy on T1. My 11-year old has been on the Dexcom for 3 weeks. For a newly diagnosed kid, it removes a lot of anxiety (and for his parents, too!) Plus, he is thrilled his meter has a Super Bowl commercial!” tweeted @KatisJewell.

Another positive tweet, from @rturnerroy, read: “@nickjonas Thank you for bringing representation to #type1diabetes. And hey #Dexcom, you’re the best.”

But many others were critical, both of Jonas and Dexcom. @hb_herrick tweeted: “Diabetes awareness is fantastic. Dexcom being able to afford Nick Jonas for a #SuperBowl commercial is not. This is a health care product. Make it more affordable for those who need it.”

Another Twitter user, @universeofdust, tweeted: “Feeling ambivalent about the #Dexcom ad tbh. I love the awareness & representation. But also not a big fan of dexcom spending $5.5 mill+ to make the CGM seem like this ~cool & trendy~ thing when many type 1s can’t afford their insulin, let alone a CGM.”

And @andricheli wrote: “Only people lucky enough to have excellent insurance and be able to afford the out-of-pocket costs have access. Many others do not.”

And in another tweet the same user said, “The #Dexcom is an amazing device. It’s literally lifesaving and life extending. But it’s also very expensive and not available to everyone. Maybe instead of spending $5 mil on a Super Bowl ad, @dexcom should spend that on getting Dex into the handle of people who need it.”

Others, including @1hitwonderdate, criticized Mr. Jonas directly, asking him: “As someone who has struggled with diabetes and is trying to support themselves along with millions of others, why not use this platform to help those who can’t afford their supplies or are rationing them?!”


 

Dexcom and Jonas’ organization respond

This news organization reached out to both Dexcom and to Beyond Type 1, a nonprofit organization cofounded by Mr. Jonas, for comment. Both emailed responses.

Regarding the intended audience for the ad, Dexcom acknowledged that it hoped to reach a much wider group than just people with type 1 diabetes or even just insulin users.

“We believe our CGM technology has the ability to empower any person with diabetes and significantly improve their treatment and quality of life, whether they are using insulin or not,” the company said, adding that the ad was also aimed at “loved ones, caregivers, and even health care professionals who need to know about this technology.”

According to Dexcom, the G6 is covered by 99% of commercial insurance in the United States, in addition to Medicare, and by Medicaid in more than 40 states. Over 70% of Dexcom patients with pharmacy coverage in the United States pay under $60 per month for CGM, and a third pay $0 out-of-pocket.

“That said, we know there’s more to be done to improve access, and we are working with several partners to broaden access to Dexcom CGM, especially for people with type 2 diabetes not on mealtime insulin,” the company noted.

Beyond Type 1 responded to the criticisms about Mr. Jonas personally, noting that the celebrity is, in fact, heavily involved in advocacy.

“Nick was involved in the launch of GetInsulin.org this past October,” they said. “GetInsulin.org is a tool created by Beyond Type 1 to connect people with diabetes in the United States to the insulin access and affordability options that match their unique circumstances. ... Beyond Type 1 will continue driving awareness of short-term solutions related to insulin access and affordability while fighting for systemic change.”

The organization “is also advocating for systemic payment policies that will make devices less expensive and avoid the same pitfalls (and rising prices) as the drug pricing system in the U.S.”

Mr. Jonas himself appears aware of the concerns.

Is 2021’s most expensive Super Bowl ad justified?

Meanwhile, in a piece in Esquire, Dave Holmes, who has type 1 diabetes, weighs up the pros and cons of the ad.

He writes: “While Jonas makes it look fun and easy to use a Dexcom G6 – a program to just get with like you would a drone or LED eyelashes – the process of acquiring one is complicated and often very expensive, even for people with good insurance. Which makes the year’s most expensive ad buy, for a product that only a small percentage of the U.S. population needs, confusing to me and others.”

Mr. Holmes also spoke with Craig Stubing, founder of the Beta Cell Foundation, a nonprofit that aims to educate and empower those with type 1 diabetes.

“Spending all this money on an ad, when people’s lives are at stake. I don’t know if offensive is the right word, but it seems out of touch with the reality that their patients are facing,” Mr. Stubing told Mr. Holmes.

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

The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.

“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.

The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.

“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.

However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”

Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.

“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.

However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”

Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.

Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.

And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.

In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
 

‘Pressing need’ to address obesity; semaglutide filed for obesity

There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.

Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.

In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”

Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.

Topline results from STEP 1 were presented June 4, 2020.

And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.

The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
 

Most patients had 5% weight loss with semaglutide

The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m² or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.

Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).

On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.

Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.

Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).

Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).

At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).

Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).

About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.

Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.

In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
 

GI disorders and ‘important limitations’

More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).

More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.

Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.

Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.

The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.

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

The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.

“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.

The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.

“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.

However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”

Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.

“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.

However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”

Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.

Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.

And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.

In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
 

‘Pressing need’ to address obesity; semaglutide filed for obesity

There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.

Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.

In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”

Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.

Topline results from STEP 1 were presented June 4, 2020.

And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.

The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
 

Most patients had 5% weight loss with semaglutide

The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m² or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.

Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).

On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.

Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.

Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).

Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).

At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).

Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).

About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.

Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.

In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
 

GI disorders and ‘important limitations’

More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).

More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.

Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.

Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.

The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.

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

The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.

“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.

The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.

“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.

However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”

Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.

“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.

However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”

Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.

Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.

And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.

In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
 

‘Pressing need’ to address obesity; semaglutide filed for obesity

There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.

Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.

In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”

Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.

Topline results from STEP 1 were presented June 4, 2020.

And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.

The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
 

Most patients had 5% weight loss with semaglutide

The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m² or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.

Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).

On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.

Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.

Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).

Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).

At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).

Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).

About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.

Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.

In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
 

GI disorders and ‘important limitations’

More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).

More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.

Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.

Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.

The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.

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

The Food and Drug Administration has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying medication in patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), the agency and Regeneron have announced.

Evinacumab had received orphan drug designation and underwent priority regulatory review based primarily on the phase 3 ELIPSE trial, presented at a meeting in March 2020 and published in August 2020 in the New England Journal of Medicine (doi: 10.1056/NEJMoa2004215).

In the trial with 65 patients with HoFH on guideline-based lipid-modifying therapy, those who also received evinacumab 15 mg/kg intravenously every 4 weeks showed a nearly 50% drop in LDL cholesterol levels after 24 weeks, compared with patients given a placebo. Only 2% of patients in both groups discontinued therapy because of adverse reactions.

The drug blocks angiopoietin-like 3, itself an inhibitor of lipoprotein lipase and endothelial lipase. It therefore lowers LDL cholesterol levels by mechanisms that don’t directly involve the LDL receptor.

Regeneron estimates that about 1300 people in the United States have the homozygous genetic disorder, which can lead to LDL cholesterol levels of a 1,000 mg/dL or higher, advanced premature atherosclerosis, and extreme risk for cardiovascular events.

The drug’s average wholesale acquisition cost per patient in the United States is expected to be about $450,000 per year, the company said, adding that it has a financial support program to help qualified patients with out-of-pocket costs.

Regeneron’s announcement included a comment from dyslipidemia-therapy expert Daniel J. Rader, MD, University of Pennsylvania, Philadelphia, who called evinacumab “a potentially transformational new treatment for people with HoFH.”

The drug is currently under regulatory review for the same indication in Europe, the company said.

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

The Food and Drug Administration has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying medication in patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), the agency and Regeneron have announced.

Evinacumab had received orphan drug designation and underwent priority regulatory review based primarily on the phase 3 ELIPSE trial, presented at a meeting in March 2020 and published in August 2020 in the New England Journal of Medicine (doi: 10.1056/NEJMoa2004215).

In the trial with 65 patients with HoFH on guideline-based lipid-modifying therapy, those who also received evinacumab 15 mg/kg intravenously every 4 weeks showed a nearly 50% drop in LDL cholesterol levels after 24 weeks, compared with patients given a placebo. Only 2% of patients in both groups discontinued therapy because of adverse reactions.

The drug blocks angiopoietin-like 3, itself an inhibitor of lipoprotein lipase and endothelial lipase. It therefore lowers LDL cholesterol levels by mechanisms that don’t directly involve the LDL receptor.

Regeneron estimates that about 1300 people in the United States have the homozygous genetic disorder, which can lead to LDL cholesterol levels of a 1,000 mg/dL or higher, advanced premature atherosclerosis, and extreme risk for cardiovascular events.

The drug’s average wholesale acquisition cost per patient in the United States is expected to be about $450,000 per year, the company said, adding that it has a financial support program to help qualified patients with out-of-pocket costs.

Regeneron’s announcement included a comment from dyslipidemia-therapy expert Daniel J. Rader, MD, University of Pennsylvania, Philadelphia, who called evinacumab “a potentially transformational new treatment for people with HoFH.”

The drug is currently under regulatory review for the same indication in Europe, the company said.

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

The Food and Drug Administration has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying medication in patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), the agency and Regeneron have announced.

Evinacumab had received orphan drug designation and underwent priority regulatory review based primarily on the phase 3 ELIPSE trial, presented at a meeting in March 2020 and published in August 2020 in the New England Journal of Medicine (doi: 10.1056/NEJMoa2004215).

In the trial with 65 patients with HoFH on guideline-based lipid-modifying therapy, those who also received evinacumab 15 mg/kg intravenously every 4 weeks showed a nearly 50% drop in LDL cholesterol levels after 24 weeks, compared with patients given a placebo. Only 2% of patients in both groups discontinued therapy because of adverse reactions.

The drug blocks angiopoietin-like 3, itself an inhibitor of lipoprotein lipase and endothelial lipase. It therefore lowers LDL cholesterol levels by mechanisms that don’t directly involve the LDL receptor.

Regeneron estimates that about 1300 people in the United States have the homozygous genetic disorder, which can lead to LDL cholesterol levels of a 1,000 mg/dL or higher, advanced premature atherosclerosis, and extreme risk for cardiovascular events.

The drug’s average wholesale acquisition cost per patient in the United States is expected to be about $450,000 per year, the company said, adding that it has a financial support program to help qualified patients with out-of-pocket costs.

Regeneron’s announcement included a comment from dyslipidemia-therapy expert Daniel J. Rader, MD, University of Pennsylvania, Philadelphia, who called evinacumab “a potentially transformational new treatment for people with HoFH.”

The drug is currently under regulatory review for the same indication in Europe, the company said.

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

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has updated its recommended immunization schedule for adults for 2021.

A summary of the annual update was published online Feb. 11 in the CDC’s Morbidity and Mortality Weekly Report and is available in Annals of Internal Medicine and on the CDC website.

It features a special section on vaccination during the pandemic as well as interim recommendations on administering the Pfizer-BioNtech and Moderna COVID-19 vaccines.

The authors, led by Mark S. Freedman, DVM, MPH, DACVPM, of the CDC’s National Center for Immunization and Respiratory Diseases, in Atlanta, note that this year’s recommendations for adults – persons aged 19 years and older – are largely the same as last year’s. “There have been very few changes,” Dr. Freedman said in an interview. “Changes to the schedule tables and notes were made to harmonize to the greatest extent possible the adult and child/adolescent schedules.”

Changes in the schedule include new or updated ACIP recommendations for influenza, hepatitis A, hepatitis B (Hep B), and human papillomavirus (HPV) as well as for meningococcal serogroups A, C, W, and Y (MenACYW) vaccines, meningococcal B (MenB) vaccines, and the zoster vaccine.

Vaccine-specific changes

Influenza

The schedule highlights updates to the composition of several influenza vaccines, which apply to components in both trivalent and quadrivalent formulations.

The cover page abbreviation for live attenuated influenza vaccine (LAIV) was changed to LAIV4. The abbreviation for live recombinant influenza vaccine (RIV) was changed to RIV4.

For individuals with a history of egg allergy who experience reactions other than hives, the following procedural warning has been added: “If using an influenza vaccine other than RIV4 or ccIIV4, administer in medical setting under supervision of health care provider who can recognize and manage severe allergic reactions.”

Zoster

The zoster vaccine live (Zostavax) has been removed from the schedule because it is no longer available in the United States. The recombinant zoster vaccine Shingrix remains available as a 2-dose regimen for adults aged 50 years or older.

HPV

As in previous years, HPV vaccination is routinely recommended for persons aged 11-12 years, with catch-up vaccination for those aged 26 or younger. Catch-up vaccination can be considered with shared decision making for those aged 27 through 45. In this year’s schedule, in the pregnancy column, the color pink, which formerly indicated “delay until after pregnancy,” has been replaced with red and an asterisk, indicating “vaccinate after pregnancy.”

HepB

ACIP continues to recommend vaccination of adults at risk for HepB; however, the text overlay has been changed to read, “2, 3, or 4 doses, depending on vaccine or condition.” Additionally, HepB vaccination is now routinely recommended for adults younger than 60 years with diabetes. For those with diabetes who are older than 60, shared decision making is recommended.

Meningococcal vaccine

ACIP continues to recommend routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for persons at increased risk for meningococcal disease caused by serogroups A, C, W, or Y. The MenQuadfi (MenACWY-TT) vaccine, which was first licensed in 2020, has been added to all relevant sections of MenACWY vaccines. For MenACWY booster doses, new text addresses special situations, including outbreaks.

Improvements have been made to text and layout, Dr. Freedman said. An example is the minimizing of specialized text. Other changes were made to ensure more consistent text structure and language. Various fine-tunings of color and positioning were made to the cover page and tables, and the wording of the notes sections was improved.

Vaccination in the pandemic

The updated schedule outlines guidance on the use of COVID-19 vaccines approved by the Food and Drug Administration under emergency use authorization, with interim recommendations for the Pfizer-BioNTech COVID-19 vaccine for people aged 16 and older and the Moderna COVID-19 vaccine for people aged 18 and older.

The authors stress the importance of receiving the recommended routine and catch-up immunizations notwithstanding widespread anxiety about visiting medical offices. Last spring, the CDC reported a dramatic drop in child vaccinations after the declaration of the national emergency in mid-March, a drop attributed to fear of COVID-19 exposure.

“ACIP continued to meet and make recommendations during the pandemic,” Dr. Freedman said. “Our recommendation remains that despite challenges caused by the COVID-19 pandemic, adults and their healthcare providers should follow the recommended vaccine schedule to protect against serious and sometimes deadly diseases.”

Regular vaccines can be safely administered even as COVID-19 retains its grasp on the United States. “Healthcare providers should follow the CDC’s interim guidance for the safe delivery of vaccines during the pandemic, which includes the use of personal protective equipment and physical distancing,” Dr. Freedman said.

Dr. Freedman has disclosed no relevant financial relationships. Coauthor Henry Bernstein, DO, is the editor of the Current Opinion in Pediatrics Office Pediatrics Series, is a Harvard School of Public Health faculty member, and is a member of the data safety and monitoring board for a Takeda study on intrathecal enzymes for Hunter and San Filippo syndromes. Coauthor Kevin Ault, MD, has served on the data safety and monitoring committee for ACI Clinical.
 

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

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has updated its recommended immunization schedule for adults for 2021.

A summary of the annual update was published online Feb. 11 in the CDC’s Morbidity and Mortality Weekly Report and is available in Annals of Internal Medicine and on the CDC website.

It features a special section on vaccination during the pandemic as well as interim recommendations on administering the Pfizer-BioNtech and Moderna COVID-19 vaccines.

The authors, led by Mark S. Freedman, DVM, MPH, DACVPM, of the CDC’s National Center for Immunization and Respiratory Diseases, in Atlanta, note that this year’s recommendations for adults – persons aged 19 years and older – are largely the same as last year’s. “There have been very few changes,” Dr. Freedman said in an interview. “Changes to the schedule tables and notes were made to harmonize to the greatest extent possible the adult and child/adolescent schedules.”

Changes in the schedule include new or updated ACIP recommendations for influenza, hepatitis A, hepatitis B (Hep B), and human papillomavirus (HPV) as well as for meningococcal serogroups A, C, W, and Y (MenACYW) vaccines, meningococcal B (MenB) vaccines, and the zoster vaccine.

Vaccine-specific changes

Influenza

The schedule highlights updates to the composition of several influenza vaccines, which apply to components in both trivalent and quadrivalent formulations.

The cover page abbreviation for live attenuated influenza vaccine (LAIV) was changed to LAIV4. The abbreviation for live recombinant influenza vaccine (RIV) was changed to RIV4.

For individuals with a history of egg allergy who experience reactions other than hives, the following procedural warning has been added: “If using an influenza vaccine other than RIV4 or ccIIV4, administer in medical setting under supervision of health care provider who can recognize and manage severe allergic reactions.”

Zoster

The zoster vaccine live (Zostavax) has been removed from the schedule because it is no longer available in the United States. The recombinant zoster vaccine Shingrix remains available as a 2-dose regimen for adults aged 50 years or older.

HPV

As in previous years, HPV vaccination is routinely recommended for persons aged 11-12 years, with catch-up vaccination for those aged 26 or younger. Catch-up vaccination can be considered with shared decision making for those aged 27 through 45. In this year’s schedule, in the pregnancy column, the color pink, which formerly indicated “delay until after pregnancy,” has been replaced with red and an asterisk, indicating “vaccinate after pregnancy.”

HepB

ACIP continues to recommend vaccination of adults at risk for HepB; however, the text overlay has been changed to read, “2, 3, or 4 doses, depending on vaccine or condition.” Additionally, HepB vaccination is now routinely recommended for adults younger than 60 years with diabetes. For those with diabetes who are older than 60, shared decision making is recommended.

Meningococcal vaccine

ACIP continues to recommend routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for persons at increased risk for meningococcal disease caused by serogroups A, C, W, or Y. The MenQuadfi (MenACWY-TT) vaccine, which was first licensed in 2020, has been added to all relevant sections of MenACWY vaccines. For MenACWY booster doses, new text addresses special situations, including outbreaks.

Improvements have been made to text and layout, Dr. Freedman said. An example is the minimizing of specialized text. Other changes were made to ensure more consistent text structure and language. Various fine-tunings of color and positioning were made to the cover page and tables, and the wording of the notes sections was improved.

Vaccination in the pandemic

The updated schedule outlines guidance on the use of COVID-19 vaccines approved by the Food and Drug Administration under emergency use authorization, with interim recommendations for the Pfizer-BioNTech COVID-19 vaccine for people aged 16 and older and the Moderna COVID-19 vaccine for people aged 18 and older.

The authors stress the importance of receiving the recommended routine and catch-up immunizations notwithstanding widespread anxiety about visiting medical offices. Last spring, the CDC reported a dramatic drop in child vaccinations after the declaration of the national emergency in mid-March, a drop attributed to fear of COVID-19 exposure.

“ACIP continued to meet and make recommendations during the pandemic,” Dr. Freedman said. “Our recommendation remains that despite challenges caused by the COVID-19 pandemic, adults and their healthcare providers should follow the recommended vaccine schedule to protect against serious and sometimes deadly diseases.”

Regular vaccines can be safely administered even as COVID-19 retains its grasp on the United States. “Healthcare providers should follow the CDC’s interim guidance for the safe delivery of vaccines during the pandemic, which includes the use of personal protective equipment and physical distancing,” Dr. Freedman said.

Dr. Freedman has disclosed no relevant financial relationships. Coauthor Henry Bernstein, DO, is the editor of the Current Opinion in Pediatrics Office Pediatrics Series, is a Harvard School of Public Health faculty member, and is a member of the data safety and monitoring board for a Takeda study on intrathecal enzymes for Hunter and San Filippo syndromes. Coauthor Kevin Ault, MD, has served on the data safety and monitoring committee for ACI Clinical.
 

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

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has updated its recommended immunization schedule for adults for 2021.

A summary of the annual update was published online Feb. 11 in the CDC’s Morbidity and Mortality Weekly Report and is available in Annals of Internal Medicine and on the CDC website.

It features a special section on vaccination during the pandemic as well as interim recommendations on administering the Pfizer-BioNtech and Moderna COVID-19 vaccines.

The authors, led by Mark S. Freedman, DVM, MPH, DACVPM, of the CDC’s National Center for Immunization and Respiratory Diseases, in Atlanta, note that this year’s recommendations for adults – persons aged 19 years and older – are largely the same as last year’s. “There have been very few changes,” Dr. Freedman said in an interview. “Changes to the schedule tables and notes were made to harmonize to the greatest extent possible the adult and child/adolescent schedules.”

Changes in the schedule include new or updated ACIP recommendations for influenza, hepatitis A, hepatitis B (Hep B), and human papillomavirus (HPV) as well as for meningococcal serogroups A, C, W, and Y (MenACYW) vaccines, meningococcal B (MenB) vaccines, and the zoster vaccine.

Vaccine-specific changes

Influenza

The schedule highlights updates to the composition of several influenza vaccines, which apply to components in both trivalent and quadrivalent formulations.

The cover page abbreviation for live attenuated influenza vaccine (LAIV) was changed to LAIV4. The abbreviation for live recombinant influenza vaccine (RIV) was changed to RIV4.

For individuals with a history of egg allergy who experience reactions other than hives, the following procedural warning has been added: “If using an influenza vaccine other than RIV4 or ccIIV4, administer in medical setting under supervision of health care provider who can recognize and manage severe allergic reactions.”

Zoster

The zoster vaccine live (Zostavax) has been removed from the schedule because it is no longer available in the United States. The recombinant zoster vaccine Shingrix remains available as a 2-dose regimen for adults aged 50 years or older.

HPV

As in previous years, HPV vaccination is routinely recommended for persons aged 11-12 years, with catch-up vaccination for those aged 26 or younger. Catch-up vaccination can be considered with shared decision making for those aged 27 through 45. In this year’s schedule, in the pregnancy column, the color pink, which formerly indicated “delay until after pregnancy,” has been replaced with red and an asterisk, indicating “vaccinate after pregnancy.”

HepB

ACIP continues to recommend vaccination of adults at risk for HepB; however, the text overlay has been changed to read, “2, 3, or 4 doses, depending on vaccine or condition.” Additionally, HepB vaccination is now routinely recommended for adults younger than 60 years with diabetes. For those with diabetes who are older than 60, shared decision making is recommended.

Meningococcal vaccine

ACIP continues to recommend routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for persons at increased risk for meningococcal disease caused by serogroups A, C, W, or Y. The MenQuadfi (MenACWY-TT) vaccine, which was first licensed in 2020, has been added to all relevant sections of MenACWY vaccines. For MenACWY booster doses, new text addresses special situations, including outbreaks.

Improvements have been made to text and layout, Dr. Freedman said. An example is the minimizing of specialized text. Other changes were made to ensure more consistent text structure and language. Various fine-tunings of color and positioning were made to the cover page and tables, and the wording of the notes sections was improved.

Vaccination in the pandemic

The updated schedule outlines guidance on the use of COVID-19 vaccines approved by the Food and Drug Administration under emergency use authorization, with interim recommendations for the Pfizer-BioNTech COVID-19 vaccine for people aged 16 and older and the Moderna COVID-19 vaccine for people aged 18 and older.

The authors stress the importance of receiving the recommended routine and catch-up immunizations notwithstanding widespread anxiety about visiting medical offices. Last spring, the CDC reported a dramatic drop in child vaccinations after the declaration of the national emergency in mid-March, a drop attributed to fear of COVID-19 exposure.

“ACIP continued to meet and make recommendations during the pandemic,” Dr. Freedman said. “Our recommendation remains that despite challenges caused by the COVID-19 pandemic, adults and their healthcare providers should follow the recommended vaccine schedule to protect against serious and sometimes deadly diseases.”

Regular vaccines can be safely administered even as COVID-19 retains its grasp on the United States. “Healthcare providers should follow the CDC’s interim guidance for the safe delivery of vaccines during the pandemic, which includes the use of personal protective equipment and physical distancing,” Dr. Freedman said.

Dr. Freedman has disclosed no relevant financial relationships. Coauthor Henry Bernstein, DO, is the editor of the Current Opinion in Pediatrics Office Pediatrics Series, is a Harvard School of Public Health faculty member, and is a member of the data safety and monitoring board for a Takeda study on intrathecal enzymes for Hunter and San Filippo syndromes. Coauthor Kevin Ault, MD, has served on the data safety and monitoring committee for ACI Clinical.
 

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

Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.

The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .

“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”

In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.

Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
 

Cholesterol changes in intervention vs. control group

HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).

Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.

There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
 

Funding barriers to obesity treatment

The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.

“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.

John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.

“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.

That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.

“You don’t necessarily need to be a physician to do this,” Dr. Flack said.

For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.

“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.

Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.

“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.

A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”

Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
 

Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.

The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .

“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”

In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.

Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
 

Cholesterol changes in intervention vs. control group

HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).

Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.

There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
 

Funding barriers to obesity treatment

The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.

“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.

John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.

“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.

That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.

“You don’t necessarily need to be a physician to do this,” Dr. Flack said.

For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.

“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.

Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.

“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.

A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”

Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
 

Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.

The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .

“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”

In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.

Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
 

Cholesterol changes in intervention vs. control group

HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).

Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.

There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
 

Funding barriers to obesity treatment

The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.

“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.

John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.

“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.

That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.

“You don’t necessarily need to be a physician to do this,” Dr. Flack said.

For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.

“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.

Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.

“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.

A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”

Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
 

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Large numbers of COVID-19 cases have been undetected and unreported, which has resulted in severe undercounting of the total number of people who have been infected during the pandemic, according to a new study published Monday in the journal PLOS ONE.

In the United States, the number of COVID-19 cases is likely three times that of reported cases. According to the study, more than 71 million Americans have contracted the virus during the pandemic, and 7 million were infected or potentially contagious last week.

Public health officials rely on case counts to guide decisions, so the undercounting should be considered while trying to end the pandemic.

“The estimates of actual infections reveal for the first time the true severity of COVID-19 across the U.S. and in countries worldwide,” Jungsik Noh, PhD, a bioinformatics professor at the University of Texas Southwestern Medical Center, said in a statement.

Dr. Noh and colleague Gaudenz Danuser created a computational model that uses machine-learning strategies to estimate the actual number of daily cases in the United States and the 50 most-infected countries.

The model pulls data from the Johns Hopkins University database and the COVID Tracking Project, as well as large-scale surveys conducted by the CDC and several states. The algorithm uses the number of reported deaths, which is thought to be more accurate than the number of lab-confirmed cases, as the basis for calculations.

In 25 of the 50 countries, the “actual” cumulative cases were estimated to be 5-20 times greater than the confirmed cases. In the United States, Belgium, and Brazil, about 10% of the population has contracted the coronavirus, according to the model. At the beginning of February, about 11% of the population in Pennsylvania had current infections, which was the highest rate of any state. About 0.15% of residents in Minnesota had infections, and about 2.5% of residents in New York and Texas had infections.

“Knowing the true severity in different regions will help us effectively fight against the virus spreading,” Dr. Noh said. “The currently infected population is the cause of future infections and deaths. Its actual size in a region is a crucial variable required when determining the severity of COVID-19 and building strategies against regional outbreaks.”

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

Large numbers of COVID-19 cases have been undetected and unreported, which has resulted in severe undercounting of the total number of people who have been infected during the pandemic, according to a new study published Monday in the journal PLOS ONE.

In the United States, the number of COVID-19 cases is likely three times that of reported cases. According to the study, more than 71 million Americans have contracted the virus during the pandemic, and 7 million were infected or potentially contagious last week.

Public health officials rely on case counts to guide decisions, so the undercounting should be considered while trying to end the pandemic.

“The estimates of actual infections reveal for the first time the true severity of COVID-19 across the U.S. and in countries worldwide,” Jungsik Noh, PhD, a bioinformatics professor at the University of Texas Southwestern Medical Center, said in a statement.

Dr. Noh and colleague Gaudenz Danuser created a computational model that uses machine-learning strategies to estimate the actual number of daily cases in the United States and the 50 most-infected countries.

The model pulls data from the Johns Hopkins University database and the COVID Tracking Project, as well as large-scale surveys conducted by the CDC and several states. The algorithm uses the number of reported deaths, which is thought to be more accurate than the number of lab-confirmed cases, as the basis for calculations.

In 25 of the 50 countries, the “actual” cumulative cases were estimated to be 5-20 times greater than the confirmed cases. In the United States, Belgium, and Brazil, about 10% of the population has contracted the coronavirus, according to the model. At the beginning of February, about 11% of the population in Pennsylvania had current infections, which was the highest rate of any state. About 0.15% of residents in Minnesota had infections, and about 2.5% of residents in New York and Texas had infections.

“Knowing the true severity in different regions will help us effectively fight against the virus spreading,” Dr. Noh said. “The currently infected population is the cause of future infections and deaths. Its actual size in a region is a crucial variable required when determining the severity of COVID-19 and building strategies against regional outbreaks.”

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

Large numbers of COVID-19 cases have been undetected and unreported, which has resulted in severe undercounting of the total number of people who have been infected during the pandemic, according to a new study published Monday in the journal PLOS ONE.

In the United States, the number of COVID-19 cases is likely three times that of reported cases. According to the study, more than 71 million Americans have contracted the virus during the pandemic, and 7 million were infected or potentially contagious last week.

Public health officials rely on case counts to guide decisions, so the undercounting should be considered while trying to end the pandemic.

“The estimates of actual infections reveal for the first time the true severity of COVID-19 across the U.S. and in countries worldwide,” Jungsik Noh, PhD, a bioinformatics professor at the University of Texas Southwestern Medical Center, said in a statement.

Dr. Noh and colleague Gaudenz Danuser created a computational model that uses machine-learning strategies to estimate the actual number of daily cases in the United States and the 50 most-infected countries.

The model pulls data from the Johns Hopkins University database and the COVID Tracking Project, as well as large-scale surveys conducted by the CDC and several states. The algorithm uses the number of reported deaths, which is thought to be more accurate than the number of lab-confirmed cases, as the basis for calculations.

In 25 of the 50 countries, the “actual” cumulative cases were estimated to be 5-20 times greater than the confirmed cases. In the United States, Belgium, and Brazil, about 10% of the population has contracted the coronavirus, according to the model. At the beginning of February, about 11% of the population in Pennsylvania had current infections, which was the highest rate of any state. About 0.15% of residents in Minnesota had infections, and about 2.5% of residents in New York and Texas had infections.

“Knowing the true severity in different regions will help us effectively fight against the virus spreading,” Dr. Noh said. “The currently infected population is the cause of future infections and deaths. Its actual size in a region is a crucial variable required when determining the severity of COVID-19 and building strategies against regional outbreaks.”

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

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.