CARLSBAD, CALIF. – With 11 different biologics approved for the treatment of plaque psoriasis on the market, settling on which one to prescribe can be tricky.

“When you look at the list of options it can be confusing to many clinicians in deciding which one to choose,” April W. Armstrong, MD, MPH, professor and chief of dermatology at the University of California, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery.

Dr. Armstrong

One approach is to consider how the biologics compare in short- and long-term efficacy. “Several different meta-analyses of biologics have been conducted,” which include some head-to head studies, Dr. Armstrong said. “In terms of efficacy, [biologics] are similar at the population level,” she said.

In a meta-analysis of 71 randomized, controlled trials through July 2020, Dr. Armstrong and colleagues found that in the short-term, Psoriasis Area and Severity Index (PASI) 90 response rates at 10-16 weeks from baseline were highest for ixekizumab (72.9%), risankizumab (72.5%), and brodalumab (72%). These PASI 90 responses were significantly higher than among patients on guselkumab (65%), secukinumab (65%), infliximab (56.8%), certolizumab (400 mg: 49.6%; 200 mg: 42.2%), ustekinumab (90 mg: 47.9%; weight-based: 45.7%; 45 mg: 44.6%), adalimumab (43%), tildrakizumab (200 mg: 39.7%; 100 mg: 37.2%), etanercept (18.0%), apremilast (12.4%), and dimethyl fumarate (12.2%).

In a more recent meta-analysis, Dr. Armstrong and coauthors used area under the curve (AUC) analyses to compare the cumulative clinical benefits of biologics over 1 year. They found that the placebo-adjusted normalized maximum AUC for a PASI 100 response was greatest for ixekizumab (0.436), risankizumab (0.423), and brodalumab (0.378), followed by guselkumab (0.358), secukinumab (0.324), ustekinumab (0.201), adalimumab (0.183), and etanercept (0.087).

In Dr. Armstrong’s opinion, the tumor necrosis factor (TNF) inhibitors etanercept, infliximab, adalimumab, and certolizumab “have served their purpose for plaque psoriasis over time, but these days I would probably choose either an IL [interleukin]-17 inhibitor or an IL-23 inhibitor first,” she said. Still, TNF inhibitors “are certainly good for psoriatic arthritis, and certolizumab is appropriate for patients who are pregnant or breastfeeding,” she said. “Avoid them in patients with demyelinating disease and in those with hepatitis B. They are not preferred in patients with latent TB or advanced CHF.”

Dr. Armstrong said that there are robust efficacy data for the IL-17 inhibitors ixekizumab, secukinumab, and brodalumab in psoriasis and in the peripheral and axial forms of psoriatic arthritis (PsA). “Avoid using them in patients with a personal history of inflammatory bowel disease,” she advised.

Low rates of oral candidiasis have been reported in the literature, “but this has not been issue with our approved IL-17 inhibitors so far,” she said.

The IL-23 inhibitors guselkumab, risankizumab, tildrakizumab, and ustekinumab have robust data for psoriasis efficacy, she said, and three – guselkumab, risankizumab, and ustekinumab – are also approved for PsA. “These agents have the advantage of fewer injections, and the evidence [of efficacy] for IL-23 inhibitors continues to evolve, such as in patients with psoriatic arthritis involving the spine,” Dr. Armstrong said.

She also shared how she deals with patients who fail to respond to biologics. “Do you switch drugs, or do you dose escalate?” she asked. “In most cases, the strategy for dose escalation is to shorten the interval between the injections so the dosing is delivered more frequently.” In a case of primary failure, which Dr. Armstrong defined as a patient who has never responded optimally to a biologic, consider revisiting the diagnosis. “Maybe it’s cutaneous T-cell lymphoma or some other condition, because our current IL-17 and IL-23 medications work extremely well,” she said. “So, if you have a patient who is not responding at all, I would question the diagnosis and consider a biopsy.”

She generally waits about 6 months before switching a patient to another biologic, “to see if they’re one of the late bloomers who may catch up in efficacy,” she explained. “Switching the class of biologic is another consideration.”

If a patient had responded to the biologic for a long time and then lost response – known as secondary failure – Dr. Armstrong considers dose escalation or a switch to another agent within the same class “if it helps to address comorbidities such as PsA,” she said. “You can also try across-class switching.”

Dr. Armstrong disclosed ties with AbbVie, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermira, Dermavant, EPI, Galderma, InCyte, Janssen, Leo, Lilly, Meiji, Modmed, Nimbus, Novartis, Ortho Dermatologics, Parexel, Pfizer, Regeneron, Sanofi, Suna, UCB, and Ventyx.

CARLSBAD, CALIF. – With 11 different biologics approved for the treatment of plaque psoriasis on the market, settling on which one to prescribe can be tricky.

“When you look at the list of options it can be confusing to many clinicians in deciding which one to choose,” April W. Armstrong, MD, MPH, professor and chief of dermatology at the University of California, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery.

Dr. Armstrong

One approach is to consider how the biologics compare in short- and long-term efficacy. “Several different meta-analyses of biologics have been conducted,” which include some head-to head studies, Dr. Armstrong said. “In terms of efficacy, [biologics] are similar at the population level,” she said.

In a meta-analysis of 71 randomized, controlled trials through July 2020, Dr. Armstrong and colleagues found that in the short-term, Psoriasis Area and Severity Index (PASI) 90 response rates at 10-16 weeks from baseline were highest for ixekizumab (72.9%), risankizumab (72.5%), and brodalumab (72%). These PASI 90 responses were significantly higher than among patients on guselkumab (65%), secukinumab (65%), infliximab (56.8%), certolizumab (400 mg: 49.6%; 200 mg: 42.2%), ustekinumab (90 mg: 47.9%; weight-based: 45.7%; 45 mg: 44.6%), adalimumab (43%), tildrakizumab (200 mg: 39.7%; 100 mg: 37.2%), etanercept (18.0%), apremilast (12.4%), and dimethyl fumarate (12.2%).

In a more recent meta-analysis, Dr. Armstrong and coauthors used area under the curve (AUC) analyses to compare the cumulative clinical benefits of biologics over 1 year. They found that the placebo-adjusted normalized maximum AUC for a PASI 100 response was greatest for ixekizumab (0.436), risankizumab (0.423), and brodalumab (0.378), followed by guselkumab (0.358), secukinumab (0.324), ustekinumab (0.201), adalimumab (0.183), and etanercept (0.087).

In Dr. Armstrong’s opinion, the tumor necrosis factor (TNF) inhibitors etanercept, infliximab, adalimumab, and certolizumab “have served their purpose for plaque psoriasis over time, but these days I would probably choose either an IL [interleukin]-17 inhibitor or an IL-23 inhibitor first,” she said. Still, TNF inhibitors “are certainly good for psoriatic arthritis, and certolizumab is appropriate for patients who are pregnant or breastfeeding,” she said. “Avoid them in patients with demyelinating disease and in those with hepatitis B. They are not preferred in patients with latent TB or advanced CHF.”

Dr. Armstrong said that there are robust efficacy data for the IL-17 inhibitors ixekizumab, secukinumab, and brodalumab in psoriasis and in the peripheral and axial forms of psoriatic arthritis (PsA). “Avoid using them in patients with a personal history of inflammatory bowel disease,” she advised.

Low rates of oral candidiasis have been reported in the literature, “but this has not been issue with our approved IL-17 inhibitors so far,” she said.

The IL-23 inhibitors guselkumab, risankizumab, tildrakizumab, and ustekinumab have robust data for psoriasis efficacy, she said, and three – guselkumab, risankizumab, and ustekinumab – are also approved for PsA. “These agents have the advantage of fewer injections, and the evidence [of efficacy] for IL-23 inhibitors continues to evolve, such as in patients with psoriatic arthritis involving the spine,” Dr. Armstrong said.

She also shared how she deals with patients who fail to respond to biologics. “Do you switch drugs, or do you dose escalate?” she asked. “In most cases, the strategy for dose escalation is to shorten the interval between the injections so the dosing is delivered more frequently.” In a case of primary failure, which Dr. Armstrong defined as a patient who has never responded optimally to a biologic, consider revisiting the diagnosis. “Maybe it’s cutaneous T-cell lymphoma or some other condition, because our current IL-17 and IL-23 medications work extremely well,” she said. “So, if you have a patient who is not responding at all, I would question the diagnosis and consider a biopsy.”

She generally waits about 6 months before switching a patient to another biologic, “to see if they’re one of the late bloomers who may catch up in efficacy,” she explained. “Switching the class of biologic is another consideration.”

If a patient had responded to the biologic for a long time and then lost response – known as secondary failure – Dr. Armstrong considers dose escalation or a switch to another agent within the same class “if it helps to address comorbidities such as PsA,” she said. “You can also try across-class switching.”

Dr. Armstrong disclosed ties with AbbVie, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermira, Dermavant, EPI, Galderma, InCyte, Janssen, Leo, Lilly, Meiji, Modmed, Nimbus, Novartis, Ortho Dermatologics, Parexel, Pfizer, Regeneron, Sanofi, Suna, UCB, and Ventyx.

CARLSBAD, CALIF. – With 11 different biologics approved for the treatment of plaque psoriasis on the market, settling on which one to prescribe can be tricky.

“When you look at the list of options it can be confusing to many clinicians in deciding which one to choose,” April W. Armstrong, MD, MPH, professor and chief of dermatology at the University of California, Los Angeles, said at the annual symposium of the California Society of Dermatology & Dermatologic Surgery.

Dr. Armstrong

One approach is to consider how the biologics compare in short- and long-term efficacy. “Several different meta-analyses of biologics have been conducted,” which include some head-to head studies, Dr. Armstrong said. “In terms of efficacy, [biologics] are similar at the population level,” she said.

In a meta-analysis of 71 randomized, controlled trials through July 2020, Dr. Armstrong and colleagues found that in the short-term, Psoriasis Area and Severity Index (PASI) 90 response rates at 10-16 weeks from baseline were highest for ixekizumab (72.9%), risankizumab (72.5%), and brodalumab (72%). These PASI 90 responses were significantly higher than among patients on guselkumab (65%), secukinumab (65%), infliximab (56.8%), certolizumab (400 mg: 49.6%; 200 mg: 42.2%), ustekinumab (90 mg: 47.9%; weight-based: 45.7%; 45 mg: 44.6%), adalimumab (43%), tildrakizumab (200 mg: 39.7%; 100 mg: 37.2%), etanercept (18.0%), apremilast (12.4%), and dimethyl fumarate (12.2%).

In a more recent meta-analysis, Dr. Armstrong and coauthors used area under the curve (AUC) analyses to compare the cumulative clinical benefits of biologics over 1 year. They found that the placebo-adjusted normalized maximum AUC for a PASI 100 response was greatest for ixekizumab (0.436), risankizumab (0.423), and brodalumab (0.378), followed by guselkumab (0.358), secukinumab (0.324), ustekinumab (0.201), adalimumab (0.183), and etanercept (0.087).

In Dr. Armstrong’s opinion, the tumor necrosis factor (TNF) inhibitors etanercept, infliximab, adalimumab, and certolizumab “have served their purpose for plaque psoriasis over time, but these days I would probably choose either an IL [interleukin]-17 inhibitor or an IL-23 inhibitor first,” she said. Still, TNF inhibitors “are certainly good for psoriatic arthritis, and certolizumab is appropriate for patients who are pregnant or breastfeeding,” she said. “Avoid them in patients with demyelinating disease and in those with hepatitis B. They are not preferred in patients with latent TB or advanced CHF.”

Dr. Armstrong said that there are robust efficacy data for the IL-17 inhibitors ixekizumab, secukinumab, and brodalumab in psoriasis and in the peripheral and axial forms of psoriatic arthritis (PsA). “Avoid using them in patients with a personal history of inflammatory bowel disease,” she advised.

Low rates of oral candidiasis have been reported in the literature, “but this has not been issue with our approved IL-17 inhibitors so far,” she said.

The IL-23 inhibitors guselkumab, risankizumab, tildrakizumab, and ustekinumab have robust data for psoriasis efficacy, she said, and three – guselkumab, risankizumab, and ustekinumab – are also approved for PsA. “These agents have the advantage of fewer injections, and the evidence [of efficacy] for IL-23 inhibitors continues to evolve, such as in patients with psoriatic arthritis involving the spine,” Dr. Armstrong said.

She also shared how she deals with patients who fail to respond to biologics. “Do you switch drugs, or do you dose escalate?” she asked. “In most cases, the strategy for dose escalation is to shorten the interval between the injections so the dosing is delivered more frequently.” In a case of primary failure, which Dr. Armstrong defined as a patient who has never responded optimally to a biologic, consider revisiting the diagnosis. “Maybe it’s cutaneous T-cell lymphoma or some other condition, because our current IL-17 and IL-23 medications work extremely well,” she said. “So, if you have a patient who is not responding at all, I would question the diagnosis and consider a biopsy.”

She generally waits about 6 months before switching a patient to another biologic, “to see if they’re one of the late bloomers who may catch up in efficacy,” she explained. “Switching the class of biologic is another consideration.”

If a patient had responded to the biologic for a long time and then lost response – known as secondary failure – Dr. Armstrong considers dose escalation or a switch to another agent within the same class “if it helps to address comorbidities such as PsA,” she said. “You can also try across-class switching.”

Dr. Armstrong disclosed ties with AbbVie, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermira, Dermavant, EPI, Galderma, InCyte, Janssen, Leo, Lilly, Meiji, Modmed, Nimbus, Novartis, Ortho Dermatologics, Parexel, Pfizer, Regeneron, Sanofi, Suna, UCB, and Ventyx.

PHILADELPHIA – Both a pelvic yoga program and a general physical conditioning program for incontinence led to improvements in women’s incontinence, according to a study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“As clinicians, we’re usually focused on treatments that we ourselves can prescribe, perform, or administer. We’re not as good as recommending or supporting treatment or management strategies that don’t rely on costly or intensive visits with clinical specialists,” lead author Alison Huang, MD, MAS, a professor of medicine at the University of California, San Francisco, said in an interview.

“But our findings suggest that women who try pelvic yoga as a complementary management strategy for genitourinary conditions like urinary incontinence that often emerge in midlife are likely to experience substantial improvement in their genitourinary symptoms and function,” Dr. Huang said. “Some of these improvements may be shared with other forms of low-impact physical movement or exercise.”

The 240 participants from communities around three Northern California sites ranged in age from 45 to 90 years old, with an average age of 62, and all had at least daily urgency, stress, or mixed-type urinary incontinence. While most were White women, 40% identified as racial/ethnic minorities, including 14% Hispanic, 6% Black, 16% Asian American, and 4% multiracial.

Participants needed to be able to walk two blocks on level ground and get from a supine to a standing position on their own, but they should not have recently participated in any organized yoga or physical conditioning exercise classes. They also needed to forgo behavioral, invasive, or pharmacologic treatments for urinary incontinence for at least 3 months. The trial ran from 2019 to 2022, with most women completing the 3-month program virtually once the pandemic began.

The 121 women randomly assigned to the pelvic yoga program had twice-weekly group instruction by trained yoga instructors and once-weekly individual practice. The practice focused on 16 standard Hatha yoga poses in standing, seated, supine, and prone positions with an emphasis on precise alignment of their postures during each pose. Yoga props, such as blocks, straps, or bolsters, were available to minimize risk of injury and to accommodate women with less flexibility.

The 119 women randomly assigned to the physical conditioning group spent the same amount of group and individual class time on skeletal muscle stretching and strengthening exercises. These exercises focused on strengthening and stretching exercises for the upper and lower extremities in standing, sitting, or supine positions. The only props needed were exercise straps and handles and an exercise mat, and the program was designed to be safe and feasible for women across all ages.

Both groups received standard self-management pamphlets describing pelvic floor muscle exercises and recommendations on timed urination and urging suppression. After early dropouts from both arms, 107 women remained for analysis in the pelvic yoga group, and 113 women remained for analysis in the physical conditioning group.

Researchers assessed participants’ genitourinary quality of life at baseline and after 3 months using the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC). At baseline, the women’s average scores were 38.8 on the UDI-6, 101 on the IIQ, and 3.4 on the PPBC.

About one-third of the women in both groups attended all 24 group classes, and 57% of women in both groups attended 20-23 classes. In addition, 65% of the women in the pelvic yoga group and 73% of the women in the physical conditioning group completed all of the recommended additional hours of individual practice. Only 15% of pelvic yoga participants and 9% of physical conditioning participants completed less than 80% of the recommended individual practice hours. No differences in participation between the groups were statistically significant.

“Over 3 months, scores on all genitourinary quality of life measures improved by more than the minimum important difference thresholds in the pelvic yoga group,” the researchers reported, but only the UDI-6 score improved significantly – albeit still modestly – in the pelvic yoga group, compared with the physical conditioning group. Average scores improved 18.9 points in the pelvic yoga group and 13.1 points in the physical conditioning group (5.8-point difference; P = .02).

The scores on the IIQ improved an average 38.5 points in the pelvic yoga group and 31.4 points in the physical conditioning group (P = .48). PPBC scores improved 0.7 points in both groups.

“While yoga may offer benefits for genitourinary quality of life, it may not offer superior benefits compared to equivalent-time practice of other activities that improve general physical function,” Dr. Huang told attendees.

“The bottom line is that physical activity toward incontinence is a helpful technique,” Stephanie Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health and medical director for the Menopause Society, said in an interview regarding the findings. Urinary incontinence is under-recognized, Dr. Faubion said, “because women are embarrassed, so they don’t bring it up, so it doesn’t get managed.” But it’s a common problem, so clinicians need to ask patients about it, she said.

“We should realize that, in midlife and older age, genitourinary health is often connected to overall health,” Dr. Huang said in an interview. “We shouldn’t focus exclusively on treatments that are directed solely at the genital or lower urinary tract organs or tissues. We should consider the ways in which women’s urinary and sexual function are influenced by other aspects of their physical and cognitive health.”

The research was funded by the National Institutes of Health. Dr. Huang and Dr. Faubion had no disclosures.

PHILADELPHIA – Both a pelvic yoga program and a general physical conditioning program for incontinence led to improvements in women’s incontinence, according to a study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“As clinicians, we’re usually focused on treatments that we ourselves can prescribe, perform, or administer. We’re not as good as recommending or supporting treatment or management strategies that don’t rely on costly or intensive visits with clinical specialists,” lead author Alison Huang, MD, MAS, a professor of medicine at the University of California, San Francisco, said in an interview.

“But our findings suggest that women who try pelvic yoga as a complementary management strategy for genitourinary conditions like urinary incontinence that often emerge in midlife are likely to experience substantial improvement in their genitourinary symptoms and function,” Dr. Huang said. “Some of these improvements may be shared with other forms of low-impact physical movement or exercise.”

The 240 participants from communities around three Northern California sites ranged in age from 45 to 90 years old, with an average age of 62, and all had at least daily urgency, stress, or mixed-type urinary incontinence. While most were White women, 40% identified as racial/ethnic minorities, including 14% Hispanic, 6% Black, 16% Asian American, and 4% multiracial.

Participants needed to be able to walk two blocks on level ground and get from a supine to a standing position on their own, but they should not have recently participated in any organized yoga or physical conditioning exercise classes. They also needed to forgo behavioral, invasive, or pharmacologic treatments for urinary incontinence for at least 3 months. The trial ran from 2019 to 2022, with most women completing the 3-month program virtually once the pandemic began.

The 121 women randomly assigned to the pelvic yoga program had twice-weekly group instruction by trained yoga instructors and once-weekly individual practice. The practice focused on 16 standard Hatha yoga poses in standing, seated, supine, and prone positions with an emphasis on precise alignment of their postures during each pose. Yoga props, such as blocks, straps, or bolsters, were available to minimize risk of injury and to accommodate women with less flexibility.

The 119 women randomly assigned to the physical conditioning group spent the same amount of group and individual class time on skeletal muscle stretching and strengthening exercises. These exercises focused on strengthening and stretching exercises for the upper and lower extremities in standing, sitting, or supine positions. The only props needed were exercise straps and handles and an exercise mat, and the program was designed to be safe and feasible for women across all ages.

Both groups received standard self-management pamphlets describing pelvic floor muscle exercises and recommendations on timed urination and urging suppression. After early dropouts from both arms, 107 women remained for analysis in the pelvic yoga group, and 113 women remained for analysis in the physical conditioning group.

Researchers assessed participants’ genitourinary quality of life at baseline and after 3 months using the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC). At baseline, the women’s average scores were 38.8 on the UDI-6, 101 on the IIQ, and 3.4 on the PPBC.

About one-third of the women in both groups attended all 24 group classes, and 57% of women in both groups attended 20-23 classes. In addition, 65% of the women in the pelvic yoga group and 73% of the women in the physical conditioning group completed all of the recommended additional hours of individual practice. Only 15% of pelvic yoga participants and 9% of physical conditioning participants completed less than 80% of the recommended individual practice hours. No differences in participation between the groups were statistically significant.

“Over 3 months, scores on all genitourinary quality of life measures improved by more than the minimum important difference thresholds in the pelvic yoga group,” the researchers reported, but only the UDI-6 score improved significantly – albeit still modestly – in the pelvic yoga group, compared with the physical conditioning group. Average scores improved 18.9 points in the pelvic yoga group and 13.1 points in the physical conditioning group (5.8-point difference; P = .02).

The scores on the IIQ improved an average 38.5 points in the pelvic yoga group and 31.4 points in the physical conditioning group (P = .48). PPBC scores improved 0.7 points in both groups.

“While yoga may offer benefits for genitourinary quality of life, it may not offer superior benefits compared to equivalent-time practice of other activities that improve general physical function,” Dr. Huang told attendees.

“The bottom line is that physical activity toward incontinence is a helpful technique,” Stephanie Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health and medical director for the Menopause Society, said in an interview regarding the findings. Urinary incontinence is under-recognized, Dr. Faubion said, “because women are embarrassed, so they don’t bring it up, so it doesn’t get managed.” But it’s a common problem, so clinicians need to ask patients about it, she said.

“We should realize that, in midlife and older age, genitourinary health is often connected to overall health,” Dr. Huang said in an interview. “We shouldn’t focus exclusively on treatments that are directed solely at the genital or lower urinary tract organs or tissues. We should consider the ways in which women’s urinary and sexual function are influenced by other aspects of their physical and cognitive health.”

The research was funded by the National Institutes of Health. Dr. Huang and Dr. Faubion had no disclosures.

PHILADELPHIA – Both a pelvic yoga program and a general physical conditioning program for incontinence led to improvements in women’s incontinence, according to a study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“As clinicians, we’re usually focused on treatments that we ourselves can prescribe, perform, or administer. We’re not as good as recommending or supporting treatment or management strategies that don’t rely on costly or intensive visits with clinical specialists,” lead author Alison Huang, MD, MAS, a professor of medicine at the University of California, San Francisco, said in an interview.

“But our findings suggest that women who try pelvic yoga as a complementary management strategy for genitourinary conditions like urinary incontinence that often emerge in midlife are likely to experience substantial improvement in their genitourinary symptoms and function,” Dr. Huang said. “Some of these improvements may be shared with other forms of low-impact physical movement or exercise.”

The 240 participants from communities around three Northern California sites ranged in age from 45 to 90 years old, with an average age of 62, and all had at least daily urgency, stress, or mixed-type urinary incontinence. While most were White women, 40% identified as racial/ethnic minorities, including 14% Hispanic, 6% Black, 16% Asian American, and 4% multiracial.

Participants needed to be able to walk two blocks on level ground and get from a supine to a standing position on their own, but they should not have recently participated in any organized yoga or physical conditioning exercise classes. They also needed to forgo behavioral, invasive, or pharmacologic treatments for urinary incontinence for at least 3 months. The trial ran from 2019 to 2022, with most women completing the 3-month program virtually once the pandemic began.

The 121 women randomly assigned to the pelvic yoga program had twice-weekly group instruction by trained yoga instructors and once-weekly individual practice. The practice focused on 16 standard Hatha yoga poses in standing, seated, supine, and prone positions with an emphasis on precise alignment of their postures during each pose. Yoga props, such as blocks, straps, or bolsters, were available to minimize risk of injury and to accommodate women with less flexibility.

The 119 women randomly assigned to the physical conditioning group spent the same amount of group and individual class time on skeletal muscle stretching and strengthening exercises. These exercises focused on strengthening and stretching exercises for the upper and lower extremities in standing, sitting, or supine positions. The only props needed were exercise straps and handles and an exercise mat, and the program was designed to be safe and feasible for women across all ages.

Both groups received standard self-management pamphlets describing pelvic floor muscle exercises and recommendations on timed urination and urging suppression. After early dropouts from both arms, 107 women remained for analysis in the pelvic yoga group, and 113 women remained for analysis in the physical conditioning group.

Researchers assessed participants’ genitourinary quality of life at baseline and after 3 months using the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC). At baseline, the women’s average scores were 38.8 on the UDI-6, 101 on the IIQ, and 3.4 on the PPBC.

About one-third of the women in both groups attended all 24 group classes, and 57% of women in both groups attended 20-23 classes. In addition, 65% of the women in the pelvic yoga group and 73% of the women in the physical conditioning group completed all of the recommended additional hours of individual practice. Only 15% of pelvic yoga participants and 9% of physical conditioning participants completed less than 80% of the recommended individual practice hours. No differences in participation between the groups were statistically significant.

“Over 3 months, scores on all genitourinary quality of life measures improved by more than the minimum important difference thresholds in the pelvic yoga group,” the researchers reported, but only the UDI-6 score improved significantly – albeit still modestly – in the pelvic yoga group, compared with the physical conditioning group. Average scores improved 18.9 points in the pelvic yoga group and 13.1 points in the physical conditioning group (5.8-point difference; P = .02).

The scores on the IIQ improved an average 38.5 points in the pelvic yoga group and 31.4 points in the physical conditioning group (P = .48). PPBC scores improved 0.7 points in both groups.

“While yoga may offer benefits for genitourinary quality of life, it may not offer superior benefits compared to equivalent-time practice of other activities that improve general physical function,” Dr. Huang told attendees.

“The bottom line is that physical activity toward incontinence is a helpful technique,” Stephanie Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health and medical director for the Menopause Society, said in an interview regarding the findings. Urinary incontinence is under-recognized, Dr. Faubion said, “because women are embarrassed, so they don’t bring it up, so it doesn’t get managed.” But it’s a common problem, so clinicians need to ask patients about it, she said.

“We should realize that, in midlife and older age, genitourinary health is often connected to overall health,” Dr. Huang said in an interview. “We shouldn’t focus exclusively on treatments that are directed solely at the genital or lower urinary tract organs or tissues. We should consider the ways in which women’s urinary and sexual function are influenced by other aspects of their physical and cognitive health.”

The research was funded by the National Institutes of Health. Dr. Huang and Dr. Faubion had no disclosures.

It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.

The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).

Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.

In HFrEF, the four medications “clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days,” Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.

“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
 

So, why is that?

The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.

Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.

Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.

The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.

For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.

But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.

The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”

The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”

For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.

“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”

What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.
 

Hospital as opportunity

The patient’s 4-7 days in the hospital typically represent a “wonderful opportunity” to initiate all four drug classes in rapid succession and start uptitrations. But most hospitals and other health care settings, Dr. Vaduganathan observed, lack the structure and systems to support the process. Broad application will require “buy-in from multiple parties – from the clinician, from the patient, their caregivers, and their partners as well as the health system.”

Physician awareness and support for the strategy, suggests at least one of these experts, is probably much less of a challenge to its broad adoption than the bewildering mechanics of health care delivery and reimbursement.

“The problem is not education. The problem is the way that our health care system is structured,” said Milton Packer, MD, Baylor Heart and Vascular Institute, Dallas.

For example, sacubitril-valsartan and the SGLT2 inhibitors are still under patent and are far more expensive than longtime generic beta-blockers and MRAs. That means physicians typically spend valuable time pursuing prior authorizations for the brand-name drugs under pressure to eventually discharge the patient because of limits on hospital reimbursement.

Clinicians in the hospital are “almost disincentivized by the system” to implement management plans that call for early and rapid initiation of multiple drugs, Dr. Vaduganathan pointed out.
 

One change per day

There’s no one formula for carrying out the quadruple drug strategy, Dr. Vaduganathan noted. “I make only a single change per day” to the regimen, such as uptitration or addition of a single agent. That way, tolerability can be evaluated one drug at a time, “and then the following day, I can make the next therapeutic change.”

The order in which the drugs are started mostly does not matter, in contrast to a traditional approach that might have added new drugs in the sequence of their approval for HFrEF or adoption in guidelines. Under that scenario, each successive agent might be fully uptitrated before the next could be brought on board.

Historically, Dr. Packer observed, “you would start with an ACE inhibitor, add a beta-blocker, add an MRA, switch to sacubitril-valsartan, add an SGLT2 inhibitor – and it would take 8 months.” Any prescribed sequence is pointless given the short time frame that is ideal for initiating all the drugs, he said.

Hypothetically, however, there is some rationale for starting them in an order that leverages their unique actions and side effects. For example, Dr. Vaduganathan and others observed, it may be helpful to start an SGLT2 inhibitor and sacubitril-valsartan early in the process, because they can mitigate any hyperkalemia from the subsequent addition of an MRA.

That being said, “I don’t think we have firm evidence that any particular order is more efficacious than another,” Dr. Vaduganathan said. “It’s really about getting patients on all four drugs as quickly as possible, regardless of the sequence.”

Discussions about sequencing the drugs are “a distraction for our field,” Dr. Greene said. In trials, clinical benefit from the multiple-drug regimen has emerged almost right away once the drugs were on board. “The data clearly show that initiating all four, at least at low doses, gives the best bang for your buck and would be a high-yield strategy.”

Best evidence suggests that once all four agents have been started, attention can turn to uptitration, “with the beta-blocker as the higher priority,” Dr. Greene said. “The bottom line is to keep it simple: four drugs, simultaneously or within 1 week, and prioritize initiation at low doses to maximize tolerability.”

The four-drug approach yields survival and rehospitalization benefits even when uptitrations don’t reach prespecified goals, Dr. Fonarow observed. The SGLT2 inhibitors are started and maintained at the same dosage. But for the other three agents, uptitration should aim for the highest well-tolerated level, up to the target, even if the highest tolerated is the initial dosage.
 

‘Challenging to generalize’

The goal in STRONG-HF was to start and at least partly uptitrate a beta-blocker, an MRA, and sacubitril-valsartan in the hospital and fully optimize their dosages within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were closely monitored at four in-person evaluations during the first 6 outpatient weeks.

But few believe the trial’s intensive drug regimen and postdischarge follow-up, as stipulated in the protocol, would be tolerated by current systems of care and reimbursement.

STRONG-HF “affirms the strategy in a rigorous, well conducted way,” Dr. Vaduganathan said, but would be “challenging to generalize to all health care systems.”

As a result, some in the field are “quick to almost disregard STRONG-HF in its entirety” and consider it “wishful thinking,” Dr. Greene said. Better that providers not become distracted by the precise details of its protocol.

At Duke, he said, “we see all our patients within 1 week of discharge to ensure they’re doing okay in terms of volume status and look for opportunities to escalate their guideline-directed medical therapy.”

But that can be done without in-person visits. A lot of the follow-up and uptitrations, Dr. Greene said, can be achieved by telephone or at virtual appointments in conjunction with regular laboratory testing. “That, I think, really is the path for the future, in this age when clinics are overwhelmed by in-person visits.”
 

Mildly reduced and preserved EF

STRONG-HF, in which patients were enrolled without regard to ejection fraction, suggests that its rapidly sequential drug regimen and intensive management protocol improves outcomes for patients with HF at any level of LVEF.

Those findings and others, along with DELIVER, EMPEROR-Preserved and other studies, make a tantalizing case for the quadruple drug approach in patients with HF and LVEF >40% – that is, those with mildly reduced (LVEF > 40% to < 50%, HFmrEF) or preserved LVEF > 50%, HFpEF) ejection fraction.

But the case isn’t solid enough to declare the four agents as core therapy for HF and LVEF > 40%, observed Dr. Vaduganathan. Currently, SGLT2 inhibitors “are the only drug class that we are routinely implementing” in HFmrEF and HFpEF.

There have been suggestions of clinical benefit for such patients with sacubitril-valsartan and MRAs, especially in PARAGON-HF and TOPCAT, respectively. The evidence is stronger in HFmrEF than in HFpEF, but in either case it’s weaker than the clear-cut trial support for SGLT2 inhibitors in those HF categories.

Trials also suggest that in HF with LVEF > 40%, clinical benefits from RAS inhibitors and MRAs taper off with increasing ejection fraction, especially into the > 60% range.

In both HFmrEF and HFpEF, “I routinely try to get the patient on an SGLT2 inhibitor rapidly and then treat with some of the other agents on a more individual basis,” Dr. Vaduganathan said. An LVEF in the HFmrEF range, for example, would likely call for the addition of an MRA and sacubitril-valsartan.

Dr. Packer said he would likely recommend all four agents for patients with HF and LVEF up to 60%, which he considers a more appropriate definition of HFrEF. Their clinical benefits appear consistent across that LVEF range, he said, although they thin out somewhat at the higher end.

Evidence supporting the four pillars in HF with LV > 40% and < 60% is weakest for beta-blockers, Dr. Packer noted, so arguably those drugs could be left out of the mix for patients with ejection fractions in that range.

Dr. Fonarow reported ties with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr. Greene disclosed ties with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon Merck, Novartis, Pfizer, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals. Dr. Vaduganathan disclosed ties with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Occlutech, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Dr. Packer disclosed relationships with 89bio, AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra.
 

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

It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.

The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).

Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.

In HFrEF, the four medications “clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days,” Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.

“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
 

So, why is that?

The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.

Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.

Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.

The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.

For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.

But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.

The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”

The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”

For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.

“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”

What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.
 

Hospital as opportunity

The patient’s 4-7 days in the hospital typically represent a “wonderful opportunity” to initiate all four drug classes in rapid succession and start uptitrations. But most hospitals and other health care settings, Dr. Vaduganathan observed, lack the structure and systems to support the process. Broad application will require “buy-in from multiple parties – from the clinician, from the patient, their caregivers, and their partners as well as the health system.”

Physician awareness and support for the strategy, suggests at least one of these experts, is probably much less of a challenge to its broad adoption than the bewildering mechanics of health care delivery and reimbursement.

“The problem is not education. The problem is the way that our health care system is structured,” said Milton Packer, MD, Baylor Heart and Vascular Institute, Dallas.

For example, sacubitril-valsartan and the SGLT2 inhibitors are still under patent and are far more expensive than longtime generic beta-blockers and MRAs. That means physicians typically spend valuable time pursuing prior authorizations for the brand-name drugs under pressure to eventually discharge the patient because of limits on hospital reimbursement.

Clinicians in the hospital are “almost disincentivized by the system” to implement management plans that call for early and rapid initiation of multiple drugs, Dr. Vaduganathan pointed out.
 

One change per day

There’s no one formula for carrying out the quadruple drug strategy, Dr. Vaduganathan noted. “I make only a single change per day” to the regimen, such as uptitration or addition of a single agent. That way, tolerability can be evaluated one drug at a time, “and then the following day, I can make the next therapeutic change.”

The order in which the drugs are started mostly does not matter, in contrast to a traditional approach that might have added new drugs in the sequence of their approval for HFrEF or adoption in guidelines. Under that scenario, each successive agent might be fully uptitrated before the next could be brought on board.

Historically, Dr. Packer observed, “you would start with an ACE inhibitor, add a beta-blocker, add an MRA, switch to sacubitril-valsartan, add an SGLT2 inhibitor – and it would take 8 months.” Any prescribed sequence is pointless given the short time frame that is ideal for initiating all the drugs, he said.

Hypothetically, however, there is some rationale for starting them in an order that leverages their unique actions and side effects. For example, Dr. Vaduganathan and others observed, it may be helpful to start an SGLT2 inhibitor and sacubitril-valsartan early in the process, because they can mitigate any hyperkalemia from the subsequent addition of an MRA.

That being said, “I don’t think we have firm evidence that any particular order is more efficacious than another,” Dr. Vaduganathan said. “It’s really about getting patients on all four drugs as quickly as possible, regardless of the sequence.”

Discussions about sequencing the drugs are “a distraction for our field,” Dr. Greene said. In trials, clinical benefit from the multiple-drug regimen has emerged almost right away once the drugs were on board. “The data clearly show that initiating all four, at least at low doses, gives the best bang for your buck and would be a high-yield strategy.”

Best evidence suggests that once all four agents have been started, attention can turn to uptitration, “with the beta-blocker as the higher priority,” Dr. Greene said. “The bottom line is to keep it simple: four drugs, simultaneously or within 1 week, and prioritize initiation at low doses to maximize tolerability.”

The four-drug approach yields survival and rehospitalization benefits even when uptitrations don’t reach prespecified goals, Dr. Fonarow observed. The SGLT2 inhibitors are started and maintained at the same dosage. But for the other three agents, uptitration should aim for the highest well-tolerated level, up to the target, even if the highest tolerated is the initial dosage.
 

‘Challenging to generalize’

The goal in STRONG-HF was to start and at least partly uptitrate a beta-blocker, an MRA, and sacubitril-valsartan in the hospital and fully optimize their dosages within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were closely monitored at four in-person evaluations during the first 6 outpatient weeks.

But few believe the trial’s intensive drug regimen and postdischarge follow-up, as stipulated in the protocol, would be tolerated by current systems of care and reimbursement.

STRONG-HF “affirms the strategy in a rigorous, well conducted way,” Dr. Vaduganathan said, but would be “challenging to generalize to all health care systems.”

As a result, some in the field are “quick to almost disregard STRONG-HF in its entirety” and consider it “wishful thinking,” Dr. Greene said. Better that providers not become distracted by the precise details of its protocol.

At Duke, he said, “we see all our patients within 1 week of discharge to ensure they’re doing okay in terms of volume status and look for opportunities to escalate their guideline-directed medical therapy.”

But that can be done without in-person visits. A lot of the follow-up and uptitrations, Dr. Greene said, can be achieved by telephone or at virtual appointments in conjunction with regular laboratory testing. “That, I think, really is the path for the future, in this age when clinics are overwhelmed by in-person visits.”
 

Mildly reduced and preserved EF

STRONG-HF, in which patients were enrolled without regard to ejection fraction, suggests that its rapidly sequential drug regimen and intensive management protocol improves outcomes for patients with HF at any level of LVEF.

Those findings and others, along with DELIVER, EMPEROR-Preserved and other studies, make a tantalizing case for the quadruple drug approach in patients with HF and LVEF >40% – that is, those with mildly reduced (LVEF > 40% to < 50%, HFmrEF) or preserved LVEF > 50%, HFpEF) ejection fraction.

But the case isn’t solid enough to declare the four agents as core therapy for HF and LVEF > 40%, observed Dr. Vaduganathan. Currently, SGLT2 inhibitors “are the only drug class that we are routinely implementing” in HFmrEF and HFpEF.

There have been suggestions of clinical benefit for such patients with sacubitril-valsartan and MRAs, especially in PARAGON-HF and TOPCAT, respectively. The evidence is stronger in HFmrEF than in HFpEF, but in either case it’s weaker than the clear-cut trial support for SGLT2 inhibitors in those HF categories.

Trials also suggest that in HF with LVEF > 40%, clinical benefits from RAS inhibitors and MRAs taper off with increasing ejection fraction, especially into the > 60% range.

In both HFmrEF and HFpEF, “I routinely try to get the patient on an SGLT2 inhibitor rapidly and then treat with some of the other agents on a more individual basis,” Dr. Vaduganathan said. An LVEF in the HFmrEF range, for example, would likely call for the addition of an MRA and sacubitril-valsartan.

Dr. Packer said he would likely recommend all four agents for patients with HF and LVEF up to 60%, which he considers a more appropriate definition of HFrEF. Their clinical benefits appear consistent across that LVEF range, he said, although they thin out somewhat at the higher end.

Evidence supporting the four pillars in HF with LV > 40% and < 60% is weakest for beta-blockers, Dr. Packer noted, so arguably those drugs could be left out of the mix for patients with ejection fractions in that range.

Dr. Fonarow reported ties with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr. Greene disclosed ties with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon Merck, Novartis, Pfizer, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals. Dr. Vaduganathan disclosed ties with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Occlutech, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Dr. Packer disclosed relationships with 89bio, AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra.
 

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

It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.

The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).

Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.

In HFrEF, the four medications “clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days,” Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.

“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
 

So, why is that?

The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.

Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.

Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.

The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.

For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.

But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.

The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”

The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”

For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.

“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”

What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.
 

Hospital as opportunity

The patient’s 4-7 days in the hospital typically represent a “wonderful opportunity” to initiate all four drug classes in rapid succession and start uptitrations. But most hospitals and other health care settings, Dr. Vaduganathan observed, lack the structure and systems to support the process. Broad application will require “buy-in from multiple parties – from the clinician, from the patient, their caregivers, and their partners as well as the health system.”

Physician awareness and support for the strategy, suggests at least one of these experts, is probably much less of a challenge to its broad adoption than the bewildering mechanics of health care delivery and reimbursement.

“The problem is not education. The problem is the way that our health care system is structured,” said Milton Packer, MD, Baylor Heart and Vascular Institute, Dallas.

For example, sacubitril-valsartan and the SGLT2 inhibitors are still under patent and are far more expensive than longtime generic beta-blockers and MRAs. That means physicians typically spend valuable time pursuing prior authorizations for the brand-name drugs under pressure to eventually discharge the patient because of limits on hospital reimbursement.

Clinicians in the hospital are “almost disincentivized by the system” to implement management plans that call for early and rapid initiation of multiple drugs, Dr. Vaduganathan pointed out.
 

One change per day

There’s no one formula for carrying out the quadruple drug strategy, Dr. Vaduganathan noted. “I make only a single change per day” to the regimen, such as uptitration or addition of a single agent. That way, tolerability can be evaluated one drug at a time, “and then the following day, I can make the next therapeutic change.”

The order in which the drugs are started mostly does not matter, in contrast to a traditional approach that might have added new drugs in the sequence of their approval for HFrEF or adoption in guidelines. Under that scenario, each successive agent might be fully uptitrated before the next could be brought on board.

Historically, Dr. Packer observed, “you would start with an ACE inhibitor, add a beta-blocker, add an MRA, switch to sacubitril-valsartan, add an SGLT2 inhibitor – and it would take 8 months.” Any prescribed sequence is pointless given the short time frame that is ideal for initiating all the drugs, he said.

Hypothetically, however, there is some rationale for starting them in an order that leverages their unique actions and side effects. For example, Dr. Vaduganathan and others observed, it may be helpful to start an SGLT2 inhibitor and sacubitril-valsartan early in the process, because they can mitigate any hyperkalemia from the subsequent addition of an MRA.

That being said, “I don’t think we have firm evidence that any particular order is more efficacious than another,” Dr. Vaduganathan said. “It’s really about getting patients on all four drugs as quickly as possible, regardless of the sequence.”

Discussions about sequencing the drugs are “a distraction for our field,” Dr. Greene said. In trials, clinical benefit from the multiple-drug regimen has emerged almost right away once the drugs were on board. “The data clearly show that initiating all four, at least at low doses, gives the best bang for your buck and would be a high-yield strategy.”

Best evidence suggests that once all four agents have been started, attention can turn to uptitration, “with the beta-blocker as the higher priority,” Dr. Greene said. “The bottom line is to keep it simple: four drugs, simultaneously or within 1 week, and prioritize initiation at low doses to maximize tolerability.”

The four-drug approach yields survival and rehospitalization benefits even when uptitrations don’t reach prespecified goals, Dr. Fonarow observed. The SGLT2 inhibitors are started and maintained at the same dosage. But for the other three agents, uptitration should aim for the highest well-tolerated level, up to the target, even if the highest tolerated is the initial dosage.
 

‘Challenging to generalize’

The goal in STRONG-HF was to start and at least partly uptitrate a beta-blocker, an MRA, and sacubitril-valsartan in the hospital and fully optimize their dosages within 2 weeks after discharge. Symptoms and laboratory biomarkers, including natriuretic peptides, were closely monitored at four in-person evaluations during the first 6 outpatient weeks.

But few believe the trial’s intensive drug regimen and postdischarge follow-up, as stipulated in the protocol, would be tolerated by current systems of care and reimbursement.

STRONG-HF “affirms the strategy in a rigorous, well conducted way,” Dr. Vaduganathan said, but would be “challenging to generalize to all health care systems.”

As a result, some in the field are “quick to almost disregard STRONG-HF in its entirety” and consider it “wishful thinking,” Dr. Greene said. Better that providers not become distracted by the precise details of its protocol.

At Duke, he said, “we see all our patients within 1 week of discharge to ensure they’re doing okay in terms of volume status and look for opportunities to escalate their guideline-directed medical therapy.”

But that can be done without in-person visits. A lot of the follow-up and uptitrations, Dr. Greene said, can be achieved by telephone or at virtual appointments in conjunction with regular laboratory testing. “That, I think, really is the path for the future, in this age when clinics are overwhelmed by in-person visits.”
 

Mildly reduced and preserved EF

STRONG-HF, in which patients were enrolled without regard to ejection fraction, suggests that its rapidly sequential drug regimen and intensive management protocol improves outcomes for patients with HF at any level of LVEF.

Those findings and others, along with DELIVER, EMPEROR-Preserved and other studies, make a tantalizing case for the quadruple drug approach in patients with HF and LVEF >40% – that is, those with mildly reduced (LVEF > 40% to < 50%, HFmrEF) or preserved LVEF > 50%, HFpEF) ejection fraction.

But the case isn’t solid enough to declare the four agents as core therapy for HF and LVEF > 40%, observed Dr. Vaduganathan. Currently, SGLT2 inhibitors “are the only drug class that we are routinely implementing” in HFmrEF and HFpEF.

There have been suggestions of clinical benefit for such patients with sacubitril-valsartan and MRAs, especially in PARAGON-HF and TOPCAT, respectively. The evidence is stronger in HFmrEF than in HFpEF, but in either case it’s weaker than the clear-cut trial support for SGLT2 inhibitors in those HF categories.

Trials also suggest that in HF with LVEF > 40%, clinical benefits from RAS inhibitors and MRAs taper off with increasing ejection fraction, especially into the > 60% range.

In both HFmrEF and HFpEF, “I routinely try to get the patient on an SGLT2 inhibitor rapidly and then treat with some of the other agents on a more individual basis,” Dr. Vaduganathan said. An LVEF in the HFmrEF range, for example, would likely call for the addition of an MRA and sacubitril-valsartan.

Dr. Packer said he would likely recommend all four agents for patients with HF and LVEF up to 60%, which he considers a more appropriate definition of HFrEF. Their clinical benefits appear consistent across that LVEF range, he said, although they thin out somewhat at the higher end.

Evidence supporting the four pillars in HF with LV > 40% and < 60% is weakest for beta-blockers, Dr. Packer noted, so arguably those drugs could be left out of the mix for patients with ejection fractions in that range.

Dr. Fonarow reported ties with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr. Greene disclosed ties with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Lilly, Bristol-Myers Squibb, Corteria, CSL Vifor, Cytokinetics, Lexicon Merck, Novartis, Pfizer, PharmaIN, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals. Dr. Vaduganathan disclosed ties with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Galmed, Impulse Dynamics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Occlutech, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health. Dr. Packer disclosed relationships with 89bio, AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Attralus, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Medtronic, Moderna, Novartis, Pharmacosmos, Reata, Regeneron, Relypsa, and Salamandra.
 

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

On Oct. 6, the Food and Drug Administration approved the use of topical roflumilast cream 0.3% for the treatment of plaque psoriasis, including intertriginous areas, for children ages 6-11. This marks an expanded indication for the drug, which was first approved for the same indication in July, 2022, for individuals aged 12 and older.

Roflumilast cream 0.3% is a phosphodiesterase-4 inhibitor approved for once-daily topical treatment of mild, moderate, and severe plaque psoriasis. According to a press release from the manufacturer, Arcutis Biotherapeutics, approval of the expanded indication is based on data from a 4-week Maximal Usage Systemic Exposure (MUSE) study in children ages 6-11 years with plaque psoriasis. It stated that pharmacokinetic, safety, tolerability, and efficacy data from this study were “generally consistent” with data from the DERMIS-1 and DERMIS-2 pivotal phase 3 trials in adults.

According to the press release, a future FDA review is planned for the results from a second MUSE study in children ages 2-5 years, as well as data from an ongoing open-label extension study evaluating the long-term safety of roflumilast cream in individuals with plaque psoriasis aged 2 years and older. The company markets topical roflumilast as Zoryve.








 

On Oct. 6, the Food and Drug Administration approved the use of topical roflumilast cream 0.3% for the treatment of plaque psoriasis, including intertriginous areas, for children ages 6-11. This marks an expanded indication for the drug, which was first approved for the same indication in July, 2022, for individuals aged 12 and older.

Roflumilast cream 0.3% is a phosphodiesterase-4 inhibitor approved for once-daily topical treatment of mild, moderate, and severe plaque psoriasis. According to a press release from the manufacturer, Arcutis Biotherapeutics, approval of the expanded indication is based on data from a 4-week Maximal Usage Systemic Exposure (MUSE) study in children ages 6-11 years with plaque psoriasis. It stated that pharmacokinetic, safety, tolerability, and efficacy data from this study were “generally consistent” with data from the DERMIS-1 and DERMIS-2 pivotal phase 3 trials in adults.

According to the press release, a future FDA review is planned for the results from a second MUSE study in children ages 2-5 years, as well as data from an ongoing open-label extension study evaluating the long-term safety of roflumilast cream in individuals with plaque psoriasis aged 2 years and older. The company markets topical roflumilast as Zoryve.








 

On Oct. 6, the Food and Drug Administration approved the use of topical roflumilast cream 0.3% for the treatment of plaque psoriasis, including intertriginous areas, for children ages 6-11. This marks an expanded indication for the drug, which was first approved for the same indication in July, 2022, for individuals aged 12 and older.

Roflumilast cream 0.3% is a phosphodiesterase-4 inhibitor approved for once-daily topical treatment of mild, moderate, and severe plaque psoriasis. According to a press release from the manufacturer, Arcutis Biotherapeutics, approval of the expanded indication is based on data from a 4-week Maximal Usage Systemic Exposure (MUSE) study in children ages 6-11 years with plaque psoriasis. It stated that pharmacokinetic, safety, tolerability, and efficacy data from this study were “generally consistent” with data from the DERMIS-1 and DERMIS-2 pivotal phase 3 trials in adults.

According to the press release, a future FDA review is planned for the results from a second MUSE study in children ages 2-5 years, as well as data from an ongoing open-label extension study evaluating the long-term safety of roflumilast cream in individuals with plaque psoriasis aged 2 years and older. The company markets topical roflumilast as Zoryve.








 

TOPLINE:

Almost one-quarter of pregnant women who have had a heart transplant (HT) will experience severe maternal morbidity (SMM) during their hospital stay for delivery, and they have sevenfold greater risk for preterm birth than do other pregnant women, results of a large study with a nationwide sample suggest.

METHODOLOGY:

• The retrospective cohort study included 2010-2020 information from the Nationwide Readmissions Database (NRD), a large, all-payer administrative dataset that allows for tracking of patient hospital readmissions in the same U.S. state within the same calendar year and includes patient demographics, hospital characteristics, diagnosis and procedure codes (including for cardiac transplants), length of stay, and discharge disposition.
• The primary outcome was nontransfusion SMM which, among other conditions, included acute myocardial infarction, aortic aneurysm, acute renal failure, adult respiratory distress syndrome, amniotic fluid embolism, cardiac arrest/ventricular fibrillation, and heart failure/arrest, during the delivery hospitalization.
• Additional outcomes included rates of all SMMs (including transfusion), a composite cardiovascular SMM (cSMM) outcome that included acute myocardial infarction, aortic aneurysm, cardiac arrest/ventricular fibrillation, cardioversion, and acute heart failure, preterm birth, and readmission rates.

TAKEAWAY:

• From 2010 to 2020, there were 19,399,521 hospital deliveries, of which, 105 were in HT recipients.
• In unadjusted comparisons, rates of all outcomes were higher in HT, compared with non-HT delivery hospitalizations, and after adjusting for age, demographic and facility characteristics, comorbid conditions, and calendar year, HT recipients continued to have higher odds of adverse maternal outcomes. For example, HT recipients had higher rates of nontransfusion SMM (adjusted odds ratio, 28.12; 95% confidence interval, 15.65-50.53), all SMM (aOR, 15.73; 95% CI, 9.17-27.00), cSMM (aOR, 37.7; 95% CI, 17.39-82.01), and preterm birth (aOR, 7.15; 95%, CI 4.75-10.77).
• HT recipients also had longer hospital stays and higher rates of cesarean delivery, although the authors noted that it’s unclear whether this increase was caused by the HT or complications of pregnancy because data were unavailable regarding indication for cesareans.
• Patients with HT were also at increased risk for hospital readmission within the first year after delivery, particularly within the first 6 months, including for HT-related complications, a finding that supports guidelines recommending an initial postpartum visit within 7-14 days of discharge for patients with cardiac conditions, write the authors.

IN PRACTICE:

The findings demonstrate the importance of counseling HT patients at early gestational ages “to provide information about anticipated risks in pregnancy and the postpartum period to allow patients the opportunity to make informed choices regarding their reproductive options,” the authors conclude.

SOURCE:

The study was conducted by Amanda M. Craig, MD, division of maternal fetal medicine, department of obstetrics and gynecology, Duke University Medical Center, Durham, N.C., and colleagues. It was published online in JACC Heart Failure.

LIMITATIONS:

Relying on diagnosis and procedure codes in administrative datasets like NRD may result in underestimation of outcomes. In this study, outcomes were limited to delivery hospitalizations, which may underestimate the true incidence of complications or fail to include pregnancies that didn’t end in a delivery, including pregnancy terminations or spontaneous abortions. Information related to race, ethnicity, hospital regions, and cause of death are not captured in the NRD dataset.

DISCLOSURES:

The authors have no relevant conflicts of interest.

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

TOPLINE:

Almost one-quarter of pregnant women who have had a heart transplant (HT) will experience severe maternal morbidity (SMM) during their hospital stay for delivery, and they have sevenfold greater risk for preterm birth than do other pregnant women, results of a large study with a nationwide sample suggest.

METHODOLOGY:

• The retrospective cohort study included 2010-2020 information from the Nationwide Readmissions Database (NRD), a large, all-payer administrative dataset that allows for tracking of patient hospital readmissions in the same U.S. state within the same calendar year and includes patient demographics, hospital characteristics, diagnosis and procedure codes (including for cardiac transplants), length of stay, and discharge disposition.
• The primary outcome was nontransfusion SMM which, among other conditions, included acute myocardial infarction, aortic aneurysm, acute renal failure, adult respiratory distress syndrome, amniotic fluid embolism, cardiac arrest/ventricular fibrillation, and heart failure/arrest, during the delivery hospitalization.
• Additional outcomes included rates of all SMMs (including transfusion), a composite cardiovascular SMM (cSMM) outcome that included acute myocardial infarction, aortic aneurysm, cardiac arrest/ventricular fibrillation, cardioversion, and acute heart failure, preterm birth, and readmission rates.

TAKEAWAY:

• From 2010 to 2020, there were 19,399,521 hospital deliveries, of which, 105 were in HT recipients.
• In unadjusted comparisons, rates of all outcomes were higher in HT, compared with non-HT delivery hospitalizations, and after adjusting for age, demographic and facility characteristics, comorbid conditions, and calendar year, HT recipients continued to have higher odds of adverse maternal outcomes. For example, HT recipients had higher rates of nontransfusion SMM (adjusted odds ratio, 28.12; 95% confidence interval, 15.65-50.53), all SMM (aOR, 15.73; 95% CI, 9.17-27.00), cSMM (aOR, 37.7; 95% CI, 17.39-82.01), and preterm birth (aOR, 7.15; 95%, CI 4.75-10.77).
• HT recipients also had longer hospital stays and higher rates of cesarean delivery, although the authors noted that it’s unclear whether this increase was caused by the HT or complications of pregnancy because data were unavailable regarding indication for cesareans.
• Patients with HT were also at increased risk for hospital readmission within the first year after delivery, particularly within the first 6 months, including for HT-related complications, a finding that supports guidelines recommending an initial postpartum visit within 7-14 days of discharge for patients with cardiac conditions, write the authors.

IN PRACTICE:

The findings demonstrate the importance of counseling HT patients at early gestational ages “to provide information about anticipated risks in pregnancy and the postpartum period to allow patients the opportunity to make informed choices regarding their reproductive options,” the authors conclude.

SOURCE:

The study was conducted by Amanda M. Craig, MD, division of maternal fetal medicine, department of obstetrics and gynecology, Duke University Medical Center, Durham, N.C., and colleagues. It was published online in JACC Heart Failure.

LIMITATIONS:

Relying on diagnosis and procedure codes in administrative datasets like NRD may result in underestimation of outcomes. In this study, outcomes were limited to delivery hospitalizations, which may underestimate the true incidence of complications or fail to include pregnancies that didn’t end in a delivery, including pregnancy terminations or spontaneous abortions. Information related to race, ethnicity, hospital regions, and cause of death are not captured in the NRD dataset.

DISCLOSURES:

The authors have no relevant conflicts of interest.

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

TOPLINE:

Almost one-quarter of pregnant women who have had a heart transplant (HT) will experience severe maternal morbidity (SMM) during their hospital stay for delivery, and they have sevenfold greater risk for preterm birth than do other pregnant women, results of a large study with a nationwide sample suggest.

METHODOLOGY:

• The retrospective cohort study included 2010-2020 information from the Nationwide Readmissions Database (NRD), a large, all-payer administrative dataset that allows for tracking of patient hospital readmissions in the same U.S. state within the same calendar year and includes patient demographics, hospital characteristics, diagnosis and procedure codes (including for cardiac transplants), length of stay, and discharge disposition.
• The primary outcome was nontransfusion SMM which, among other conditions, included acute myocardial infarction, aortic aneurysm, acute renal failure, adult respiratory distress syndrome, amniotic fluid embolism, cardiac arrest/ventricular fibrillation, and heart failure/arrest, during the delivery hospitalization.
• Additional outcomes included rates of all SMMs (including transfusion), a composite cardiovascular SMM (cSMM) outcome that included acute myocardial infarction, aortic aneurysm, cardiac arrest/ventricular fibrillation, cardioversion, and acute heart failure, preterm birth, and readmission rates.

TAKEAWAY:

• From 2010 to 2020, there were 19,399,521 hospital deliveries, of which, 105 were in HT recipients.
• In unadjusted comparisons, rates of all outcomes were higher in HT, compared with non-HT delivery hospitalizations, and after adjusting for age, demographic and facility characteristics, comorbid conditions, and calendar year, HT recipients continued to have higher odds of adverse maternal outcomes. For example, HT recipients had higher rates of nontransfusion SMM (adjusted odds ratio, 28.12; 95% confidence interval, 15.65-50.53), all SMM (aOR, 15.73; 95% CI, 9.17-27.00), cSMM (aOR, 37.7; 95% CI, 17.39-82.01), and preterm birth (aOR, 7.15; 95%, CI 4.75-10.77).
• HT recipients also had longer hospital stays and higher rates of cesarean delivery, although the authors noted that it’s unclear whether this increase was caused by the HT or complications of pregnancy because data were unavailable regarding indication for cesareans.
• Patients with HT were also at increased risk for hospital readmission within the first year after delivery, particularly within the first 6 months, including for HT-related complications, a finding that supports guidelines recommending an initial postpartum visit within 7-14 days of discharge for patients with cardiac conditions, write the authors.

IN PRACTICE:

The findings demonstrate the importance of counseling HT patients at early gestational ages “to provide information about anticipated risks in pregnancy and the postpartum period to allow patients the opportunity to make informed choices regarding their reproductive options,” the authors conclude.

SOURCE:

The study was conducted by Amanda M. Craig, MD, division of maternal fetal medicine, department of obstetrics and gynecology, Duke University Medical Center, Durham, N.C., and colleagues. It was published online in JACC Heart Failure.

LIMITATIONS:

Relying on diagnosis and procedure codes in administrative datasets like NRD may result in underestimation of outcomes. In this study, outcomes were limited to delivery hospitalizations, which may underestimate the true incidence of complications or fail to include pregnancies that didn’t end in a delivery, including pregnancy terminations or spontaneous abortions. Information related to race, ethnicity, hospital regions, and cause of death are not captured in the NRD dataset.

DISCLOSURES:

The authors have no relevant conflicts of interest.

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

HAMBURG, GERMANY – Respiratory tract infections and asthma are 10 times more prevalent at type 2 diabetes diagnosis, compared with matched controls without a diagnosis, shows a longitudinal study looking at comorbidities both 25 years before and 25 years after a type 2 diabetes diagnosis.

About 40% of people had respiratory tract infections at the time of diagnosis with type 2 diabetes, compared with 4% who were not diagnosed. Likewise, ear, nose, and throat infections were present in 20% of people at type 2 diabetes diagnosis, compared with around 2% who were not diagnosed. A similar pattern was seen with asthma.

Taken together, the data suggest that subacute inflammation manifesting in asthma as well as the onset of asthma or an acute infection may be a precursor to a type 2 diabetes diagnosis.

“We have also found that in the years prior to diagnosis, there are associations with infections and inflammatory disorders to a much greater degree than in those people who do not get a diabetes diagnosis but who have very similar demographics,” Adrian Heald, MD, study lead and diabetes consultant from Salford (England) Royal Hospital, said in an interview.

Five years prior to diagnosis, respiratory tract infections were documented in around 23% of patients who were later diagnosed with type 2 diabetes versus 2.5% in those not diagnosed, and a similar pattern was seen for ear, nose, and throat infections and asthma. The findings suggest that patients reporting infections, in addition to other known risk factors for type 2 diabetes, might benefit from diabetes tests and early interventions, if needed.

“These novel insights offer a fascinating and fresh perspective on the onset and natural progression to type 2 diabetes and beyond, suggesting an early phase of inflammation-related disease activity long before any clinical diagnosis of type 2 diabetes is made.”

Dr. Heald points out that clinicians may intervene to stave off progression to a type 2 diabetes diagnosis in at risk patients. “At this point, an intervention could relate to lifestyle changes and involve highlighting to the patient that the morbidity they have already accumulated is suggestive of diabetes risk,” he said, adding that, “they may have dyslipidemia, hypertension, and most often excess weight so annual checks of their HbA1c, weight management, and blood pressure would need checking,” he explained.

Moderator Coen Stehouwer, MD, professor of internal medicine at Maastricht University, the Netherlands, commented, “Before clinical diagnosis of type 2 diabetes there is often a lengthy period of undiagnosed disease and before that, prediabetes, because glucose can be abnormal up to 10 years prior to clinical diagnosis.”

But he added that, “It’s not entirely clear whether the rise seen before clinical diagnosis in this study correlates with undiagnosed diabetes or prediabetes or even if it precedes type 2 diabetes – it might be because inflammation is a common origin for type 2 diabetes and various comorbidities. This might explain how they go together.”
 

Longitudinal study 25 years before and 25 years after type 2 diagnosis

Dr. Heald presented the findings at a session on inflammation in diabetes at the annual meeting of the European Association for the Study of Diabetes. The work was also published in Diabetes Therapy.

The researchers wanted to investigate the pattern of comorbidities in the years and decades prior to a diagnosis of type 2 diabetes as well as after: “With the database we used, called DARE [Diabetes Alliance for Research in England], we are able to explore phenomena longitudinally going right back to the beginning of their digital health records, looking at phenotypes over time.”

By mapping significant health issues in people who went on to develop type 2 diabetes alongside those that did not, Dr. Heald managed to develop a continuum spanning 25 years prior and 25 years after diagnosis of type 2 diabetes. The researchers also examined relationships between sociodemographic factors and longitudinal health outcomes of relevance to cardiac conditions and lower respiratory tract infections. His talk in Hamburg primarily addressed clinical phenotypes before the point of diagnosis.

Data were drawn from 1,932 people with (1,196) and without (736) type 2 diabetes. Participants in both groups were aged 66-67 years, 43%-46% were women, age at diagnosis was 50-52 years, and participants lived in Greater Manchester, United Kingdom.

In the years leading up to type 2 diagnosis, individuals consistently exhibited a considerable increase in several clinical phenotypes, reported Dr. Heald. Of note, he added, “immediately prior to type 2 diagnosis, there was a significantly greater proportion of hypertension at 35%, respiratory tract infection at 34%, heart disease at 17%, ear, nose, and throat infection at 19%, and asthma at 12%. And by comparison, the corresponding disease trajectory in matched controls was much less dramatic.”

“There is a huge difference in people who went on to receive a diagnosis of type 2 diabetes and those who did not, and not just what we’d expect – so hypertension for example or manifestations of renal disease, but importantly inflammatory disorders are more common,” he emphasized.

In addition, a larger signal for ischemic heart disease was seen just before type 2 diabetes diagnosis.

These data suggest that longitudinal clinical histories prior to a diagnosis of type 2 diabetes might offer new information, both genetic and nongenetic, about development of type 2 diabetes in relation to comorbidities.

After type 2 diabetes diagnosis, the proportion of people exhibiting coronary artery disease, hypertension, chronic kidney disease, retinopathy, and infections climbed rapidly before plateauing, reported Dr. Heald. “We also know that individuals with coronary artery disease are more highly represented in socially disadvantaged groups, and this is borne out in the data at 25 years prior and after type 2 diagnosis.”

Dr. Heald has received speaker fees or contributed to advisory boards from Lilly, AstraZeneca, Janssen, Bristol-Myers Squibb, Besins, Bayer, Sanofi, and Recordati. Research grants from Novo Nordisk, Pfizer, and Besins. Professor Stehouwer has declared no relevant conflicts.

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

HAMBURG, GERMANY – Respiratory tract infections and asthma are 10 times more prevalent at type 2 diabetes diagnosis, compared with matched controls without a diagnosis, shows a longitudinal study looking at comorbidities both 25 years before and 25 years after a type 2 diabetes diagnosis.

About 40% of people had respiratory tract infections at the time of diagnosis with type 2 diabetes, compared with 4% who were not diagnosed. Likewise, ear, nose, and throat infections were present in 20% of people at type 2 diabetes diagnosis, compared with around 2% who were not diagnosed. A similar pattern was seen with asthma.

Taken together, the data suggest that subacute inflammation manifesting in asthma as well as the onset of asthma or an acute infection may be a precursor to a type 2 diabetes diagnosis.

“We have also found that in the years prior to diagnosis, there are associations with infections and inflammatory disorders to a much greater degree than in those people who do not get a diabetes diagnosis but who have very similar demographics,” Adrian Heald, MD, study lead and diabetes consultant from Salford (England) Royal Hospital, said in an interview.

Five years prior to diagnosis, respiratory tract infections were documented in around 23% of patients who were later diagnosed with type 2 diabetes versus 2.5% in those not diagnosed, and a similar pattern was seen for ear, nose, and throat infections and asthma. The findings suggest that patients reporting infections, in addition to other known risk factors for type 2 diabetes, might benefit from diabetes tests and early interventions, if needed.

“These novel insights offer a fascinating and fresh perspective on the onset and natural progression to type 2 diabetes and beyond, suggesting an early phase of inflammation-related disease activity long before any clinical diagnosis of type 2 diabetes is made.”

Dr. Heald points out that clinicians may intervene to stave off progression to a type 2 diabetes diagnosis in at risk patients. “At this point, an intervention could relate to lifestyle changes and involve highlighting to the patient that the morbidity they have already accumulated is suggestive of diabetes risk,” he said, adding that, “they may have dyslipidemia, hypertension, and most often excess weight so annual checks of their HbA1c, weight management, and blood pressure would need checking,” he explained.

Moderator Coen Stehouwer, MD, professor of internal medicine at Maastricht University, the Netherlands, commented, “Before clinical diagnosis of type 2 diabetes there is often a lengthy period of undiagnosed disease and before that, prediabetes, because glucose can be abnormal up to 10 years prior to clinical diagnosis.”

But he added that, “It’s not entirely clear whether the rise seen before clinical diagnosis in this study correlates with undiagnosed diabetes or prediabetes or even if it precedes type 2 diabetes – it might be because inflammation is a common origin for type 2 diabetes and various comorbidities. This might explain how they go together.”
 

Longitudinal study 25 years before and 25 years after type 2 diagnosis

Dr. Heald presented the findings at a session on inflammation in diabetes at the annual meeting of the European Association for the Study of Diabetes. The work was also published in Diabetes Therapy.

The researchers wanted to investigate the pattern of comorbidities in the years and decades prior to a diagnosis of type 2 diabetes as well as after: “With the database we used, called DARE [Diabetes Alliance for Research in England], we are able to explore phenomena longitudinally going right back to the beginning of their digital health records, looking at phenotypes over time.”

By mapping significant health issues in people who went on to develop type 2 diabetes alongside those that did not, Dr. Heald managed to develop a continuum spanning 25 years prior and 25 years after diagnosis of type 2 diabetes. The researchers also examined relationships between sociodemographic factors and longitudinal health outcomes of relevance to cardiac conditions and lower respiratory tract infections. His talk in Hamburg primarily addressed clinical phenotypes before the point of diagnosis.

Data were drawn from 1,932 people with (1,196) and without (736) type 2 diabetes. Participants in both groups were aged 66-67 years, 43%-46% were women, age at diagnosis was 50-52 years, and participants lived in Greater Manchester, United Kingdom.

In the years leading up to type 2 diagnosis, individuals consistently exhibited a considerable increase in several clinical phenotypes, reported Dr. Heald. Of note, he added, “immediately prior to type 2 diagnosis, there was a significantly greater proportion of hypertension at 35%, respiratory tract infection at 34%, heart disease at 17%, ear, nose, and throat infection at 19%, and asthma at 12%. And by comparison, the corresponding disease trajectory in matched controls was much less dramatic.”

“There is a huge difference in people who went on to receive a diagnosis of type 2 diabetes and those who did not, and not just what we’d expect – so hypertension for example or manifestations of renal disease, but importantly inflammatory disorders are more common,” he emphasized.

In addition, a larger signal for ischemic heart disease was seen just before type 2 diabetes diagnosis.

These data suggest that longitudinal clinical histories prior to a diagnosis of type 2 diabetes might offer new information, both genetic and nongenetic, about development of type 2 diabetes in relation to comorbidities.

After type 2 diabetes diagnosis, the proportion of people exhibiting coronary artery disease, hypertension, chronic kidney disease, retinopathy, and infections climbed rapidly before plateauing, reported Dr. Heald. “We also know that individuals with coronary artery disease are more highly represented in socially disadvantaged groups, and this is borne out in the data at 25 years prior and after type 2 diagnosis.”

Dr. Heald has received speaker fees or contributed to advisory boards from Lilly, AstraZeneca, Janssen, Bristol-Myers Squibb, Besins, Bayer, Sanofi, and Recordati. Research grants from Novo Nordisk, Pfizer, and Besins. Professor Stehouwer has declared no relevant conflicts.

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

HAMBURG, GERMANY – Respiratory tract infections and asthma are 10 times more prevalent at type 2 diabetes diagnosis, compared with matched controls without a diagnosis, shows a longitudinal study looking at comorbidities both 25 years before and 25 years after a type 2 diabetes diagnosis.

About 40% of people had respiratory tract infections at the time of diagnosis with type 2 diabetes, compared with 4% who were not diagnosed. Likewise, ear, nose, and throat infections were present in 20% of people at type 2 diabetes diagnosis, compared with around 2% who were not diagnosed. A similar pattern was seen with asthma.

Taken together, the data suggest that subacute inflammation manifesting in asthma as well as the onset of asthma or an acute infection may be a precursor to a type 2 diabetes diagnosis.

“We have also found that in the years prior to diagnosis, there are associations with infections and inflammatory disorders to a much greater degree than in those people who do not get a diabetes diagnosis but who have very similar demographics,” Adrian Heald, MD, study lead and diabetes consultant from Salford (England) Royal Hospital, said in an interview.

Five years prior to diagnosis, respiratory tract infections were documented in around 23% of patients who were later diagnosed with type 2 diabetes versus 2.5% in those not diagnosed, and a similar pattern was seen for ear, nose, and throat infections and asthma. The findings suggest that patients reporting infections, in addition to other known risk factors for type 2 diabetes, might benefit from diabetes tests and early interventions, if needed.

“These novel insights offer a fascinating and fresh perspective on the onset and natural progression to type 2 diabetes and beyond, suggesting an early phase of inflammation-related disease activity long before any clinical diagnosis of type 2 diabetes is made.”

Dr. Heald points out that clinicians may intervene to stave off progression to a type 2 diabetes diagnosis in at risk patients. “At this point, an intervention could relate to lifestyle changes and involve highlighting to the patient that the morbidity they have already accumulated is suggestive of diabetes risk,” he said, adding that, “they may have dyslipidemia, hypertension, and most often excess weight so annual checks of their HbA1c, weight management, and blood pressure would need checking,” he explained.

Moderator Coen Stehouwer, MD, professor of internal medicine at Maastricht University, the Netherlands, commented, “Before clinical diagnosis of type 2 diabetes there is often a lengthy period of undiagnosed disease and before that, prediabetes, because glucose can be abnormal up to 10 years prior to clinical diagnosis.”

But he added that, “It’s not entirely clear whether the rise seen before clinical diagnosis in this study correlates with undiagnosed diabetes or prediabetes or even if it precedes type 2 diabetes – it might be because inflammation is a common origin for type 2 diabetes and various comorbidities. This might explain how they go together.”
 

Longitudinal study 25 years before and 25 years after type 2 diagnosis

Dr. Heald presented the findings at a session on inflammation in diabetes at the annual meeting of the European Association for the Study of Diabetes. The work was also published in Diabetes Therapy.

The researchers wanted to investigate the pattern of comorbidities in the years and decades prior to a diagnosis of type 2 diabetes as well as after: “With the database we used, called DARE [Diabetes Alliance for Research in England], we are able to explore phenomena longitudinally going right back to the beginning of their digital health records, looking at phenotypes over time.”

By mapping significant health issues in people who went on to develop type 2 diabetes alongside those that did not, Dr. Heald managed to develop a continuum spanning 25 years prior and 25 years after diagnosis of type 2 diabetes. The researchers also examined relationships between sociodemographic factors and longitudinal health outcomes of relevance to cardiac conditions and lower respiratory tract infections. His talk in Hamburg primarily addressed clinical phenotypes before the point of diagnosis.

Data were drawn from 1,932 people with (1,196) and without (736) type 2 diabetes. Participants in both groups were aged 66-67 years, 43%-46% were women, age at diagnosis was 50-52 years, and participants lived in Greater Manchester, United Kingdom.

In the years leading up to type 2 diagnosis, individuals consistently exhibited a considerable increase in several clinical phenotypes, reported Dr. Heald. Of note, he added, “immediately prior to type 2 diagnosis, there was a significantly greater proportion of hypertension at 35%, respiratory tract infection at 34%, heart disease at 17%, ear, nose, and throat infection at 19%, and asthma at 12%. And by comparison, the corresponding disease trajectory in matched controls was much less dramatic.”

“There is a huge difference in people who went on to receive a diagnosis of type 2 diabetes and those who did not, and not just what we’d expect – so hypertension for example or manifestations of renal disease, but importantly inflammatory disorders are more common,” he emphasized.

In addition, a larger signal for ischemic heart disease was seen just before type 2 diabetes diagnosis.

These data suggest that longitudinal clinical histories prior to a diagnosis of type 2 diabetes might offer new information, both genetic and nongenetic, about development of type 2 diabetes in relation to comorbidities.

After type 2 diabetes diagnosis, the proportion of people exhibiting coronary artery disease, hypertension, chronic kidney disease, retinopathy, and infections climbed rapidly before plateauing, reported Dr. Heald. “We also know that individuals with coronary artery disease are more highly represented in socially disadvantaged groups, and this is borne out in the data at 25 years prior and after type 2 diagnosis.”

Dr. Heald has received speaker fees or contributed to advisory boards from Lilly, AstraZeneca, Janssen, Bristol-Myers Squibb, Besins, Bayer, Sanofi, and Recordati. Research grants from Novo Nordisk, Pfizer, and Besins. Professor Stehouwer has declared no relevant conflicts.

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

WASHINGTON – Transgender female veterans are more likely to have thyroid cancer at rates comparable with cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.

“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”

To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.

“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.

“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”

Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.

“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”

Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”

Dr. Christensen and Dr. Garcia had no disclosures to report.

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

WASHINGTON – Transgender female veterans are more likely to have thyroid cancer at rates comparable with cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.

“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”

To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.

“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.

“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”

Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.

“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”

Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”

Dr. Christensen and Dr. Garcia had no disclosures to report.

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

WASHINGTON – Transgender female veterans are more likely to have thyroid cancer at rates comparable with cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.

“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”

To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.

“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.

“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”

Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.

“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”

Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”

Dr. Christensen and Dr. Garcia had no disclosures to report.

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

HAMBURG, GERMANY – An international consensus report on precision diabetes medicine aims to further move the field from aspirational to actionable with a person-first focus.

“Diabetes recommendations often focus on what works well for the average person. However, because diabetes is an incredibly heterogeneous disease, few people are Mr. or Mrs. ‘average’ and one-size-fits-all approaches fail many people in need. Precision medicine seeks to address this major problem,” said Precision Medicine in Diabetes Initiative (PDMI) cochair Paul Franks, PhD, MPhil, head of the department of translational medicine at the Novo Nordisk Foundation in Denmark.

The report is the second from the joint American Diabetes Association/European Association for the Study of Diabetes PDMI, a consortium organized in 2018 with the aim of addressing “the untenable health and economic burdens of diabetes prevention and care.”

Based on findings from 15 systematic reviews and expert opinions, the new statement covers the key precision medicine pillars of prevention, diagnosis, treatment, and prognosis for each of four major recognized forms of diabetes: monogenic, gestational, type 1, and type 2. It addresses clinical translation of precision medicine research, including near-term actionable measures. Working groups were tasked with defining the key research questions that need to be addressed for precision diabetes medicine to be implemented into clinical practice by 2030.

Dr. Franks noted that “precision medicine seeks to improve diabetes prevention and care by combining data about a person’s health or disease state and response to medications. The aim is to tailor the advice given about diabetes prevention or treatment to the person in question, rather than having them make do with generic advice. Precision medicine very much focuses on treating the person and not the disease.”

A 90-minute symposium summarizing the report was presented at the annual meeting of the European Association for the Study of Diabetes. An executive summary was simultaneously published in the journal Nature Medicine. Four additional complementary papers, covering cardiometabolic disease precision medicine, diabetes heterogeneity, precision medicine of obesity, and precision cardiometabolic medicine in low- and middle-income countries, were published separately in The Lancet Diabetes & Endocrinology.

In a comment, Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, England, called the new report “fantastic collaborative work.”

However, Dr. Khunti said, “I think at the moment we’re at the discovery stage of precision medicine. The clinical utility of that, we’ll have to see over the years.”

Dr. Khunti also pointed out: “A lot of the work done in precision medicine has been on specific diseases, like diabetes and cardiovascular disease. But, 30% of people don’t just have one disease, they have multiple long-term conditions. I think we need to start thinking about that now, rather than single conditions, because we want to look at drug targets that will hit multiple long-term conditions rather than one single condition.”
 

Currently, a dearth of data

Even just within diabetes, there is a dearth of quality data. In fact, Dr. Franks told this news organization, there has only been one precision medicine trial in diabetes, called TriMaster, comparing individual responses to three different second-line treatments for type 2 diabetes after metformin. “The problem with that trial is that the second-line medications it investigated aren’t widely prescribed now. The trial was designed back in 2014. It took a long time, then there was COVID, and by the time it was published too much time had elapsed and it was already out of date.”

Ideally, to make this effort current, Dr. Franks said, “is to get drug companies to implement these trials into their development pipelines. If you think about it, it’s far more efficient to implement precision medicine early in the drug development process than late, because when you do it late you end up having to do lots of comparisons of different possibilities. When you do it early you sort out those comparisons as part of the development process, so it really comes down to companies being willing to do that and regulators being willing to accept results from those trials. That’s another challenge, which is why we stress regulatory engagement as a key thing.”

In the future, he said, using the second-line type 2 diabetes drug as an example, when a person is diagnosed with type 2 diabetes they might automatically be given a companion diagnostic that’s more sophisticated and more precise than current ways of defining cardiovascular risk to better predict which individuals are more likely to experience a cardiovascular event.

This concept, referred to as “precision diagnostics,” is a “core driver of precision medicine,” Dr. Franks said. “If we can get a higher predictive accuracy on cardiovascular outcomes in people with diabetes, essentially treatment allocation is likely to be more precise too, because you’re not treating people you don’t need to treat and you’re not missing people you should have treated. I think that’s probably how it will work out.”
 

‘Studying diverse populations benefits everyone’

An important component emphasized in the report is the lack of “relevant, high-quality research in people of non-European ancestry, hindering the development and implementation of precision diabetes medicine in many of the most heavily burdened populations worldwide.”

That specific issue was addressed during the symposium by Shivani Misra, MBBS, PhD clinical senior lecturer in diabetes and endocrinology at Imperial College, London, and the lead author of the separate complementary paper on the topic.

Dr. Misra argued against the notion that precision medicine is only for wealthy countries, noting that diabetes and other noncommunicable diseases are becoming major health problems in low- and middle-income countries. “Resource-restricted settings may derive the greatest benefits from precision medicine,” she said. “Studying diverse populations benefits everyone.”

And worldwide, she noted, “the right drug for the right person will improve cost-effectiveness in the long-term.”

Dr. Franks is an employee of the Novo Nordisk Foundation, a “purely philanthropic enterprise-owning foundation” with a portfolio of 151 companies. He has received consultancy fees from Zoe Ltd., Eli Lilly, and Novo Nordisk, and research funding from multiple pharmaceutical companies. Dr. Khunti has acted as a consultant, speaker, or received grants for investigator-initiated studies from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie/Menarini Group, Janssen, and Napp. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation.

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

HAMBURG, GERMANY – An international consensus report on precision diabetes medicine aims to further move the field from aspirational to actionable with a person-first focus.

“Diabetes recommendations often focus on what works well for the average person. However, because diabetes is an incredibly heterogeneous disease, few people are Mr. or Mrs. ‘average’ and one-size-fits-all approaches fail many people in need. Precision medicine seeks to address this major problem,” said Precision Medicine in Diabetes Initiative (PDMI) cochair Paul Franks, PhD, MPhil, head of the department of translational medicine at the Novo Nordisk Foundation in Denmark.

The report is the second from the joint American Diabetes Association/European Association for the Study of Diabetes PDMI, a consortium organized in 2018 with the aim of addressing “the untenable health and economic burdens of diabetes prevention and care.”

Based on findings from 15 systematic reviews and expert opinions, the new statement covers the key precision medicine pillars of prevention, diagnosis, treatment, and prognosis for each of four major recognized forms of diabetes: monogenic, gestational, type 1, and type 2. It addresses clinical translation of precision medicine research, including near-term actionable measures. Working groups were tasked with defining the key research questions that need to be addressed for precision diabetes medicine to be implemented into clinical practice by 2030.

Dr. Franks noted that “precision medicine seeks to improve diabetes prevention and care by combining data about a person’s health or disease state and response to medications. The aim is to tailor the advice given about diabetes prevention or treatment to the person in question, rather than having them make do with generic advice. Precision medicine very much focuses on treating the person and not the disease.”

A 90-minute symposium summarizing the report was presented at the annual meeting of the European Association for the Study of Diabetes. An executive summary was simultaneously published in the journal Nature Medicine. Four additional complementary papers, covering cardiometabolic disease precision medicine, diabetes heterogeneity, precision medicine of obesity, and precision cardiometabolic medicine in low- and middle-income countries, were published separately in The Lancet Diabetes & Endocrinology.

In a comment, Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, England, called the new report “fantastic collaborative work.”

However, Dr. Khunti said, “I think at the moment we’re at the discovery stage of precision medicine. The clinical utility of that, we’ll have to see over the years.”

Dr. Khunti also pointed out: “A lot of the work done in precision medicine has been on specific diseases, like diabetes and cardiovascular disease. But, 30% of people don’t just have one disease, they have multiple long-term conditions. I think we need to start thinking about that now, rather than single conditions, because we want to look at drug targets that will hit multiple long-term conditions rather than one single condition.”
 

Currently, a dearth of data

Even just within diabetes, there is a dearth of quality data. In fact, Dr. Franks told this news organization, there has only been one precision medicine trial in diabetes, called TriMaster, comparing individual responses to three different second-line treatments for type 2 diabetes after metformin. “The problem with that trial is that the second-line medications it investigated aren’t widely prescribed now. The trial was designed back in 2014. It took a long time, then there was COVID, and by the time it was published too much time had elapsed and it was already out of date.”

Ideally, to make this effort current, Dr. Franks said, “is to get drug companies to implement these trials into their development pipelines. If you think about it, it’s far more efficient to implement precision medicine early in the drug development process than late, because when you do it late you end up having to do lots of comparisons of different possibilities. When you do it early you sort out those comparisons as part of the development process, so it really comes down to companies being willing to do that and regulators being willing to accept results from those trials. That’s another challenge, which is why we stress regulatory engagement as a key thing.”

In the future, he said, using the second-line type 2 diabetes drug as an example, when a person is diagnosed with type 2 diabetes they might automatically be given a companion diagnostic that’s more sophisticated and more precise than current ways of defining cardiovascular risk to better predict which individuals are more likely to experience a cardiovascular event.

This concept, referred to as “precision diagnostics,” is a “core driver of precision medicine,” Dr. Franks said. “If we can get a higher predictive accuracy on cardiovascular outcomes in people with diabetes, essentially treatment allocation is likely to be more precise too, because you’re not treating people you don’t need to treat and you’re not missing people you should have treated. I think that’s probably how it will work out.”
 

‘Studying diverse populations benefits everyone’

An important component emphasized in the report is the lack of “relevant, high-quality research in people of non-European ancestry, hindering the development and implementation of precision diabetes medicine in many of the most heavily burdened populations worldwide.”

That specific issue was addressed during the symposium by Shivani Misra, MBBS, PhD clinical senior lecturer in diabetes and endocrinology at Imperial College, London, and the lead author of the separate complementary paper on the topic.

Dr. Misra argued against the notion that precision medicine is only for wealthy countries, noting that diabetes and other noncommunicable diseases are becoming major health problems in low- and middle-income countries. “Resource-restricted settings may derive the greatest benefits from precision medicine,” she said. “Studying diverse populations benefits everyone.”

And worldwide, she noted, “the right drug for the right person will improve cost-effectiveness in the long-term.”

Dr. Franks is an employee of the Novo Nordisk Foundation, a “purely philanthropic enterprise-owning foundation” with a portfolio of 151 companies. He has received consultancy fees from Zoe Ltd., Eli Lilly, and Novo Nordisk, and research funding from multiple pharmaceutical companies. Dr. Khunti has acted as a consultant, speaker, or received grants for investigator-initiated studies from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie/Menarini Group, Janssen, and Napp. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation.

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

HAMBURG, GERMANY – An international consensus report on precision diabetes medicine aims to further move the field from aspirational to actionable with a person-first focus.

“Diabetes recommendations often focus on what works well for the average person. However, because diabetes is an incredibly heterogeneous disease, few people are Mr. or Mrs. ‘average’ and one-size-fits-all approaches fail many people in need. Precision medicine seeks to address this major problem,” said Precision Medicine in Diabetes Initiative (PDMI) cochair Paul Franks, PhD, MPhil, head of the department of translational medicine at the Novo Nordisk Foundation in Denmark.

The report is the second from the joint American Diabetes Association/European Association for the Study of Diabetes PDMI, a consortium organized in 2018 with the aim of addressing “the untenable health and economic burdens of diabetes prevention and care.”

Based on findings from 15 systematic reviews and expert opinions, the new statement covers the key precision medicine pillars of prevention, diagnosis, treatment, and prognosis for each of four major recognized forms of diabetes: monogenic, gestational, type 1, and type 2. It addresses clinical translation of precision medicine research, including near-term actionable measures. Working groups were tasked with defining the key research questions that need to be addressed for precision diabetes medicine to be implemented into clinical practice by 2030.

Dr. Franks noted that “precision medicine seeks to improve diabetes prevention and care by combining data about a person’s health or disease state and response to medications. The aim is to tailor the advice given about diabetes prevention or treatment to the person in question, rather than having them make do with generic advice. Precision medicine very much focuses on treating the person and not the disease.”

A 90-minute symposium summarizing the report was presented at the annual meeting of the European Association for the Study of Diabetes. An executive summary was simultaneously published in the journal Nature Medicine. Four additional complementary papers, covering cardiometabolic disease precision medicine, diabetes heterogeneity, precision medicine of obesity, and precision cardiometabolic medicine in low- and middle-income countries, were published separately in The Lancet Diabetes & Endocrinology.

In a comment, Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, England, called the new report “fantastic collaborative work.”

However, Dr. Khunti said, “I think at the moment we’re at the discovery stage of precision medicine. The clinical utility of that, we’ll have to see over the years.”

Dr. Khunti also pointed out: “A lot of the work done in precision medicine has been on specific diseases, like diabetes and cardiovascular disease. But, 30% of people don’t just have one disease, they have multiple long-term conditions. I think we need to start thinking about that now, rather than single conditions, because we want to look at drug targets that will hit multiple long-term conditions rather than one single condition.”
 

Currently, a dearth of data

Even just within diabetes, there is a dearth of quality data. In fact, Dr. Franks told this news organization, there has only been one precision medicine trial in diabetes, called TriMaster, comparing individual responses to three different second-line treatments for type 2 diabetes after metformin. “The problem with that trial is that the second-line medications it investigated aren’t widely prescribed now. The trial was designed back in 2014. It took a long time, then there was COVID, and by the time it was published too much time had elapsed and it was already out of date.”

Ideally, to make this effort current, Dr. Franks said, “is to get drug companies to implement these trials into their development pipelines. If you think about it, it’s far more efficient to implement precision medicine early in the drug development process than late, because when you do it late you end up having to do lots of comparisons of different possibilities. When you do it early you sort out those comparisons as part of the development process, so it really comes down to companies being willing to do that and regulators being willing to accept results from those trials. That’s another challenge, which is why we stress regulatory engagement as a key thing.”

In the future, he said, using the second-line type 2 diabetes drug as an example, when a person is diagnosed with type 2 diabetes they might automatically be given a companion diagnostic that’s more sophisticated and more precise than current ways of defining cardiovascular risk to better predict which individuals are more likely to experience a cardiovascular event.

This concept, referred to as “precision diagnostics,” is a “core driver of precision medicine,” Dr. Franks said. “If we can get a higher predictive accuracy on cardiovascular outcomes in people with diabetes, essentially treatment allocation is likely to be more precise too, because you’re not treating people you don’t need to treat and you’re not missing people you should have treated. I think that’s probably how it will work out.”
 

‘Studying diverse populations benefits everyone’

An important component emphasized in the report is the lack of “relevant, high-quality research in people of non-European ancestry, hindering the development and implementation of precision diabetes medicine in many of the most heavily burdened populations worldwide.”

That specific issue was addressed during the symposium by Shivani Misra, MBBS, PhD clinical senior lecturer in diabetes and endocrinology at Imperial College, London, and the lead author of the separate complementary paper on the topic.

Dr. Misra argued against the notion that precision medicine is only for wealthy countries, noting that diabetes and other noncommunicable diseases are becoming major health problems in low- and middle-income countries. “Resource-restricted settings may derive the greatest benefits from precision medicine,” she said. “Studying diverse populations benefits everyone.”

And worldwide, she noted, “the right drug for the right person will improve cost-effectiveness in the long-term.”

Dr. Franks is an employee of the Novo Nordisk Foundation, a “purely philanthropic enterprise-owning foundation” with a portfolio of 151 companies. He has received consultancy fees from Zoe Ltd., Eli Lilly, and Novo Nordisk, and research funding from multiple pharmaceutical companies. Dr. Khunti has acted as a consultant, speaker, or received grants for investigator-initiated studies from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie/Menarini Group, Janssen, and Napp. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation.

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

The Food and Drug Administration has granted an interchangeability designation to adalimumab-afzb (Abrilada), according to an announcement from Pfizer.

This is the second adalimumab biosimilar granted interchangeability. The first, adalimumab-adbm (Cyltezo), became available in July.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Biosimilars introduce market competition that can help lower drug prices. Adalimumab-afzb is one of nine approved biosimilars for Humira, and the last to launch in 2023.

Adalimumab-afzb is indicated for:

• Adults with rheumatoid arthritis. 
• Polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
• Adults with psoriatic arthritis.
• Adults with ankylosing spondylitis.
• Crohn’s disease in adults and children 6 years of age and older.
• Adults with ulcerative colitis.
• Adults with plaque psoriasis.
• Adults with hidradenitis suppurativa.
• Adults with noninfectious intermediate and posterior uveitis and panuveitis.

“With this designation, Abrilada is now both biosimilar to and interchangeable with Humira, reinforcing confidence among physicians and pharmacists that there is no decrease in effectiveness or increase in safety risk associated with switching between Abrilada and the reference product,” Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, Dallas, said in Pfizer’s statement.

An interchangeability designation allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). To achieve this designation, Pfizer submitted data from a phase 3 study led by Dr. Fleischmann that evaluated adalimumab-afzb in patients with RA. Patients who were switched three times between the biosimilar and the reference product had outcomes similar to those of patients continuously treated with the reference product. 

Adalimumab-afzb will be available later in October at a 5% discount from Humira’s price. Later this year, the drug will launch at a second price, a 60% discount from Humira.

Full prescribing information for adalimumab-afzb is available here.

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

The Food and Drug Administration has granted an interchangeability designation to adalimumab-afzb (Abrilada), according to an announcement from Pfizer.

This is the second adalimumab biosimilar granted interchangeability. The first, adalimumab-adbm (Cyltezo), became available in July.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Biosimilars introduce market competition that can help lower drug prices. Adalimumab-afzb is one of nine approved biosimilars for Humira, and the last to launch in 2023.

Adalimumab-afzb is indicated for:

• Adults with rheumatoid arthritis. 
• Polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
• Adults with psoriatic arthritis.
• Adults with ankylosing spondylitis.
• Crohn’s disease in adults and children 6 years of age and older.
• Adults with ulcerative colitis.
• Adults with plaque psoriasis.
• Adults with hidradenitis suppurativa.
• Adults with noninfectious intermediate and posterior uveitis and panuveitis.

“With this designation, Abrilada is now both biosimilar to and interchangeable with Humira, reinforcing confidence among physicians and pharmacists that there is no decrease in effectiveness or increase in safety risk associated with switching between Abrilada and the reference product,” Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, Dallas, said in Pfizer’s statement.

An interchangeability designation allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). To achieve this designation, Pfizer submitted data from a phase 3 study led by Dr. Fleischmann that evaluated adalimumab-afzb in patients with RA. Patients who were switched three times between the biosimilar and the reference product had outcomes similar to those of patients continuously treated with the reference product. 

Adalimumab-afzb will be available later in October at a 5% discount from Humira’s price. Later this year, the drug will launch at a second price, a 60% discount from Humira.

Full prescribing information for adalimumab-afzb is available here.

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

The Food and Drug Administration has granted an interchangeability designation to adalimumab-afzb (Abrilada), according to an announcement from Pfizer.

This is the second adalimumab biosimilar granted interchangeability. The first, adalimumab-adbm (Cyltezo), became available in July.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Biosimilars introduce market competition that can help lower drug prices. Adalimumab-afzb is one of nine approved biosimilars for Humira, and the last to launch in 2023.

Adalimumab-afzb is indicated for:

• Adults with rheumatoid arthritis. 
• Polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
• Adults with psoriatic arthritis.
• Adults with ankylosing spondylitis.
• Crohn’s disease in adults and children 6 years of age and older.
• Adults with ulcerative colitis.
• Adults with plaque psoriasis.
• Adults with hidradenitis suppurativa.
• Adults with noninfectious intermediate and posterior uveitis and panuveitis.

“With this designation, Abrilada is now both biosimilar to and interchangeable with Humira, reinforcing confidence among physicians and pharmacists that there is no decrease in effectiveness or increase in safety risk associated with switching between Abrilada and the reference product,” Roy Fleischmann, MD, clinical professor of medicine, University of Texas Southwestern Medical Center, Dallas, said in Pfizer’s statement.

An interchangeability designation allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). To achieve this designation, Pfizer submitted data from a phase 3 study led by Dr. Fleischmann that evaluated adalimumab-afzb in patients with RA. Patients who were switched three times between the biosimilar and the reference product had outcomes similar to those of patients continuously treated with the reference product. 

Adalimumab-afzb will be available later in October at a 5% discount from Humira’s price. Later this year, the drug will launch at a second price, a 60% discount from Humira.

Full prescribing information for adalimumab-afzb is available here.

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

Two antiamyloid drugs were recently approved by the Food and Drug Administration for treating early-stage Alzheimer’s disease (AD). In trials of both lecanemab (Leqembi) and donanemab, a long-held neuropharmacologic dream was realized: Most amyloid plaques – the primary pathologic marker for AD – were eliminated from the brains of patients with late pre-AD or early AD.

Implications for the amyloid hypothesis

The reduction of amyloid plaques has been argued by many scientists and clinical authorities to be the likely pharmacologic solution for AD. These trials are appropriately viewed as a test of the hypothesis that amyloid bodies are a primary cause of the neurobehavioral symptoms we call AD.

In parallel with that striking reduction in amyloid bodies, drug-treated patients had an initially slower progression of neurobehavioral decline than did placebo-treated control patients. That slowing in symptom progression was accompanied by a modest but statistically significant difference in neurobehavioral ability. After several months in treatment, the rate of decline again paralleled that recorded in the control group. The sustained difference of about a half point on cognitive assessment scores separating treatment and control participants was well short of the 1.5-point difference typically considered clinically significant.

A small number of unexpected and unexplained deaths occurred in the treatment groups. Brain swelling and/or micro-hemorrhages were seen in 20%-30% of treated individuals. Significant brain shrinkage was recorded. These adverse findings are indicative of drug-induced trauma in the target organ for these drugs (i.e., the brain) and were the basis for a boxed warning label for drug usage. Antiamyloid drug treatment was not effective in patients who had higher initial numbers of amyloid plaques, indicating that these drugs would not measurably help the majority of AD patients, who are at more advanced disease stages.

These drugs do not appear to be an “answer” for AD. A modest delay in progression does not mean that we’re on a path to a “cure.” Treatment cost estimates are high – more than $80,000 per year. With requisite PET exams and high copays, patient accessibility issues will be daunting.

Of note, in my view, the trials of these drugs do not support the hypothesis that amyloid is the primary neuropathologic agent underlying the progressive neurobehavioral decline in AD. To the contrary, they add strong support for the counterargument that the emergence of amyloid plaques is an effect and not a fundamental cause of that progressive loss of neurologic function that we ultimately define as “Alzheimer’s disease.”
 

Time to switch gears

The more obvious path to winning the battle against this human scourge is prevention. A recent analysis published in The Lancet argued that about 40% of AD and other dementias are potentially preventable. I disagree. I believe that 80%-90% of prospective cases can be substantially delayed or prevented. Studies have shown that progression to AD or other dementias is driven primarily by the progressive deterioration of organic brain health, expressed by the loss of what psychologists have termed “cognitive reserve.” Cognitive reserve is resilience arising from active brain usage, akin to physical resilience attributable to a physically active life. Scientific studies have shown us that an individual’s cognitive resilience (reserve) is a greater predictor of risk for dementia than are amyloid plaques – indeed, greater than any combination of pathologic markers in dementia patients.

Building up cognitive reserve

It’s increasingly clear to this observer that cognitive reserve is synonymous with organic brain health. The primary factors that underlie cognitive reserve are processing speed in the brain, executive control, response withholding, memory acquisition, reasoning, and attention abilities. Faster, more accurate brains are necessarily more physically optimized. They necessarily sustain brain system connectivity. They are necessarily healthier. Such brains bear a relatively low risk of developing AD or other dementias, just as physically healthier bodies bear a lower risk of being prematurely banished to semi-permanent residence in an easy chair or a bed.

Brain health can be sustained by deploying inexpensive, self-administered, app-based assessments of neurologic performance limits, which inform patients and their medical teams about general brain health status. These assessments can help doctors guide their patients to adopt more intelligent brain-healthy lifestyles, or direct them to the “brain gym” to progressively exercise their brains in ways that contribute to rapid, potentially large-scale, rejuvenating improvements in physical and functional brain health.

Randomized controlled trials incorporating different combinations of physical exercise, diet, and cognitive training have recorded significant improvements in physical and functional neurologic status, indicating substantially advanced brain health. Consistent moderate-to-intense physical exercise, brain- and heart-healthy eating habits, and, particularly, computerized brain training have repeatedly been shown to improve cognitive function and physically rejuvenate the brain. With cognitive training in the right forms, improvements in processing speed and other measures manifest improving brain health and greater safety.

In the National Institutes of Health–funded ACTIVE study with more than 2,800 older adults, just 10-18 hours of a specific speed of processing training (now part of BrainHQ, a program that I was involved in developing) reduced the probability of a progression to dementia over the following 10 years by 29%, and by 48% in those who did the most training.

This approach is several orders of magnitude less expensive than the pricey new AD drugs. It presents less serious issues of accessibility and has no side effects. It delivers far more powerful therapeutic benefits in older normal and at-risk populations.

Sustained wellness supporting prevention is the far more sensible medical way forward to save people from AD and other dementias – at a far lower medical and societal cost.

Dr. Merzenich is professor emeritus, department of neuroscience, University of California, San Francisco. He reported conflicts of interest with Posit Science, Stronger Brains, and the National Institutes of Health.

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

Two antiamyloid drugs were recently approved by the Food and Drug Administration for treating early-stage Alzheimer’s disease (AD). In trials of both lecanemab (Leqembi) and donanemab, a long-held neuropharmacologic dream was realized: Most amyloid plaques – the primary pathologic marker for AD – were eliminated from the brains of patients with late pre-AD or early AD.

Implications for the amyloid hypothesis

The reduction of amyloid plaques has been argued by many scientists and clinical authorities to be the likely pharmacologic solution for AD. These trials are appropriately viewed as a test of the hypothesis that amyloid bodies are a primary cause of the neurobehavioral symptoms we call AD.

In parallel with that striking reduction in amyloid bodies, drug-treated patients had an initially slower progression of neurobehavioral decline than did placebo-treated control patients. That slowing in symptom progression was accompanied by a modest but statistically significant difference in neurobehavioral ability. After several months in treatment, the rate of decline again paralleled that recorded in the control group. The sustained difference of about a half point on cognitive assessment scores separating treatment and control participants was well short of the 1.5-point difference typically considered clinically significant.

A small number of unexpected and unexplained deaths occurred in the treatment groups. Brain swelling and/or micro-hemorrhages were seen in 20%-30% of treated individuals. Significant brain shrinkage was recorded. These adverse findings are indicative of drug-induced trauma in the target organ for these drugs (i.e., the brain) and were the basis for a boxed warning label for drug usage. Antiamyloid drug treatment was not effective in patients who had higher initial numbers of amyloid plaques, indicating that these drugs would not measurably help the majority of AD patients, who are at more advanced disease stages.

These drugs do not appear to be an “answer” for AD. A modest delay in progression does not mean that we’re on a path to a “cure.” Treatment cost estimates are high – more than $80,000 per year. With requisite PET exams and high copays, patient accessibility issues will be daunting.

Of note, in my view, the trials of these drugs do not support the hypothesis that amyloid is the primary neuropathologic agent underlying the progressive neurobehavioral decline in AD. To the contrary, they add strong support for the counterargument that the emergence of amyloid plaques is an effect and not a fundamental cause of that progressive loss of neurologic function that we ultimately define as “Alzheimer’s disease.”
 

Time to switch gears

The more obvious path to winning the battle against this human scourge is prevention. A recent analysis published in The Lancet argued that about 40% of AD and other dementias are potentially preventable. I disagree. I believe that 80%-90% of prospective cases can be substantially delayed or prevented. Studies have shown that progression to AD or other dementias is driven primarily by the progressive deterioration of organic brain health, expressed by the loss of what psychologists have termed “cognitive reserve.” Cognitive reserve is resilience arising from active brain usage, akin to physical resilience attributable to a physically active life. Scientific studies have shown us that an individual’s cognitive resilience (reserve) is a greater predictor of risk for dementia than are amyloid plaques – indeed, greater than any combination of pathologic markers in dementia patients.

Building up cognitive reserve

It’s increasingly clear to this observer that cognitive reserve is synonymous with organic brain health. The primary factors that underlie cognitive reserve are processing speed in the brain, executive control, response withholding, memory acquisition, reasoning, and attention abilities. Faster, more accurate brains are necessarily more physically optimized. They necessarily sustain brain system connectivity. They are necessarily healthier. Such brains bear a relatively low risk of developing AD or other dementias, just as physically healthier bodies bear a lower risk of being prematurely banished to semi-permanent residence in an easy chair or a bed.

Brain health can be sustained by deploying inexpensive, self-administered, app-based assessments of neurologic performance limits, which inform patients and their medical teams about general brain health status. These assessments can help doctors guide their patients to adopt more intelligent brain-healthy lifestyles, or direct them to the “brain gym” to progressively exercise their brains in ways that contribute to rapid, potentially large-scale, rejuvenating improvements in physical and functional brain health.

Randomized controlled trials incorporating different combinations of physical exercise, diet, and cognitive training have recorded significant improvements in physical and functional neurologic status, indicating substantially advanced brain health. Consistent moderate-to-intense physical exercise, brain- and heart-healthy eating habits, and, particularly, computerized brain training have repeatedly been shown to improve cognitive function and physically rejuvenate the brain. With cognitive training in the right forms, improvements in processing speed and other measures manifest improving brain health and greater safety.

In the National Institutes of Health–funded ACTIVE study with more than 2,800 older adults, just 10-18 hours of a specific speed of processing training (now part of BrainHQ, a program that I was involved in developing) reduced the probability of a progression to dementia over the following 10 years by 29%, and by 48% in those who did the most training.

This approach is several orders of magnitude less expensive than the pricey new AD drugs. It presents less serious issues of accessibility and has no side effects. It delivers far more powerful therapeutic benefits in older normal and at-risk populations.

Sustained wellness supporting prevention is the far more sensible medical way forward to save people from AD and other dementias – at a far lower medical and societal cost.

Dr. Merzenich is professor emeritus, department of neuroscience, University of California, San Francisco. He reported conflicts of interest with Posit Science, Stronger Brains, and the National Institutes of Health.

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

Two antiamyloid drugs were recently approved by the Food and Drug Administration for treating early-stage Alzheimer’s disease (AD). In trials of both lecanemab (Leqembi) and donanemab, a long-held neuropharmacologic dream was realized: Most amyloid plaques – the primary pathologic marker for AD – were eliminated from the brains of patients with late pre-AD or early AD.

Implications for the amyloid hypothesis

The reduction of amyloid plaques has been argued by many scientists and clinical authorities to be the likely pharmacologic solution for AD. These trials are appropriately viewed as a test of the hypothesis that amyloid bodies are a primary cause of the neurobehavioral symptoms we call AD.

In parallel with that striking reduction in amyloid bodies, drug-treated patients had an initially slower progression of neurobehavioral decline than did placebo-treated control patients. That slowing in symptom progression was accompanied by a modest but statistically significant difference in neurobehavioral ability. After several months in treatment, the rate of decline again paralleled that recorded in the control group. The sustained difference of about a half point on cognitive assessment scores separating treatment and control participants was well short of the 1.5-point difference typically considered clinically significant.

A small number of unexpected and unexplained deaths occurred in the treatment groups. Brain swelling and/or micro-hemorrhages were seen in 20%-30% of treated individuals. Significant brain shrinkage was recorded. These adverse findings are indicative of drug-induced trauma in the target organ for these drugs (i.e., the brain) and were the basis for a boxed warning label for drug usage. Antiamyloid drug treatment was not effective in patients who had higher initial numbers of amyloid plaques, indicating that these drugs would not measurably help the majority of AD patients, who are at more advanced disease stages.

These drugs do not appear to be an “answer” for AD. A modest delay in progression does not mean that we’re on a path to a “cure.” Treatment cost estimates are high – more than $80,000 per year. With requisite PET exams and high copays, patient accessibility issues will be daunting.

Of note, in my view, the trials of these drugs do not support the hypothesis that amyloid is the primary neuropathologic agent underlying the progressive neurobehavioral decline in AD. To the contrary, they add strong support for the counterargument that the emergence of amyloid plaques is an effect and not a fundamental cause of that progressive loss of neurologic function that we ultimately define as “Alzheimer’s disease.”
 

Time to switch gears

The more obvious path to winning the battle against this human scourge is prevention. A recent analysis published in The Lancet argued that about 40% of AD and other dementias are potentially preventable. I disagree. I believe that 80%-90% of prospective cases can be substantially delayed or prevented. Studies have shown that progression to AD or other dementias is driven primarily by the progressive deterioration of organic brain health, expressed by the loss of what psychologists have termed “cognitive reserve.” Cognitive reserve is resilience arising from active brain usage, akin to physical resilience attributable to a physically active life. Scientific studies have shown us that an individual’s cognitive resilience (reserve) is a greater predictor of risk for dementia than are amyloid plaques – indeed, greater than any combination of pathologic markers in dementia patients.

Building up cognitive reserve

It’s increasingly clear to this observer that cognitive reserve is synonymous with organic brain health. The primary factors that underlie cognitive reserve are processing speed in the brain, executive control, response withholding, memory acquisition, reasoning, and attention abilities. Faster, more accurate brains are necessarily more physically optimized. They necessarily sustain brain system connectivity. They are necessarily healthier. Such brains bear a relatively low risk of developing AD or other dementias, just as physically healthier bodies bear a lower risk of being prematurely banished to semi-permanent residence in an easy chair or a bed.

Brain health can be sustained by deploying inexpensive, self-administered, app-based assessments of neurologic performance limits, which inform patients and their medical teams about general brain health status. These assessments can help doctors guide their patients to adopt more intelligent brain-healthy lifestyles, or direct them to the “brain gym” to progressively exercise their brains in ways that contribute to rapid, potentially large-scale, rejuvenating improvements in physical and functional brain health.

Randomized controlled trials incorporating different combinations of physical exercise, diet, and cognitive training have recorded significant improvements in physical and functional neurologic status, indicating substantially advanced brain health. Consistent moderate-to-intense physical exercise, brain- and heart-healthy eating habits, and, particularly, computerized brain training have repeatedly been shown to improve cognitive function and physically rejuvenate the brain. With cognitive training in the right forms, improvements in processing speed and other measures manifest improving brain health and greater safety.

In the National Institutes of Health–funded ACTIVE study with more than 2,800 older adults, just 10-18 hours of a specific speed of processing training (now part of BrainHQ, a program that I was involved in developing) reduced the probability of a progression to dementia over the following 10 years by 29%, and by 48% in those who did the most training.

This approach is several orders of magnitude less expensive than the pricey new AD drugs. It presents less serious issues of accessibility and has no side effects. It delivers far more powerful therapeutic benefits in older normal and at-risk populations.

Sustained wellness supporting prevention is the far more sensible medical way forward to save people from AD and other dementias – at a far lower medical and societal cost.

Dr. Merzenich is professor emeritus, department of neuroscience, University of California, San Francisco. He reported conflicts of interest with Posit Science, Stronger Brains, and the National Institutes of Health.

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