A subset of patients with HR+ metastatic breast cancer (mBC) may have primary resistance to endocrine therapy (ET), and the majority will develop progressive disease and secondary resistance at some point during their treatment course. The phase 3 PEARL trial randomly assigned 601 postmenopausal patients with HR+/HER2- mBC that was resistant to prior aromatase inhibitor therapy to capecitabine or palbociclib + ET (with exemestane or fulvestrant). There was no significant difference in OS between the palbociclib + ET and capecitabine arms in both the wild-type–ESR1 population (median OS 37.2 vs 34.8 months; adjusted HR 1.06; P = .683) and overall population (median OS 32.6 vs 30.9 months, adjusted HR 1.00; P = .995) (Martin et al). The randomized phase 2 Young-PEARL trial demonstrated a progression-free survival (PFS) benefit with palbociclib + exemestane + leuprolide vs capecitabine among 189 premenopausal women with HR+/HER2- mBC and relapse or progression on prior tamoxifen therapy (median PFS 20.1 vs 14.4 months; HR 0.659; P = .0235).² In this study, half of the patients were treatment-naive in the metastatic setting and had no prior aromatase inhibitor exposure. Considering the similar survival outcomes seen in PEARL in postmenopausal patients, the choice of therapy should include consideration of other variables, such as side effects, comorbidities, and OS results, which will be further informative in the premenopausal population.
 

Poorer outcomes associated with breast cancer in younger women (< 45 years of age) are driven by multiple factors, including delayed diagnosis, more aggressive biologic subtypes, and advanced stage at presentation. Survival outcomes for breast cancer diagnosed and treated during pregnancy are similar to nonpregnant patients. Postpartum breast cancer (PPBC) is a distinct entity, defined as breast cancer that is diagnosed within the first 5 years after childbirth, and is more likely to have inferior outcomes. A pooled data set from the Colorado Young Women Breast cohort and the Breast Cancer Health Disparities study (n = 2519 cases) showed that among women diagnosed at < 45 years, those who were nulliparous had better OS vs those with PPBC (HR 0.61), with a more prominent effect among stage I breast cancers (HR 0.30) and in very young women diagnosed at ≤ 35 years (HR 0.44) (Shagisultanova et al). At 15 years of follow-up, among very young women diagnosed at ≤ 35 years, those with PPBC had an OS of 63% compared with 71% for nulliparous women and 67% for women who had given birth more than 5 years ago. There are various factors that likely contribute to poorer outcomes seen with PPBC, including mammary gland involution and a lactation effect. Research efforts focused on aspects, such as the tumor immune microenvironment in the postpartum state, lactation studies, and perhaps identification of a postpartum signature, will enhance our understanding with the goal to optimize outcomes for young women with PPBC.^[3]
 

The treatment of male breast cancer in the advanced or metastatic setting is largely extrapolated from female studies. Registry data have shown differences in clinicopathologic characteristics between metastatic male breast cancer (mMBC) and metastatic female breast cancer (mFBC). For example, there is a higher proportion of simultaneous lung and bone involvement and a lower proportion of HER2+/HR- triple-negative subtypes, and simultaneous bone and liver metastasis in mMBC vs mFBC.⁴ An analysis including 207 male patients with breast cancer with bone metastases in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 3-year OS and cancer-specific survival (CSS) rates of 36.7% and 39.5%, respectively. Inferior OS and CSS were associated with age > 60 years (for OS: HR 1.671; P = .014; for CSS: HR 1.806; P = .009), triple-negative subtype (for OS: HR 3.029, P = .003; for CSS: HR 3.025, P = .004), and lack of surgery (for OS: HR 1.746; P = .012; for CSS: HR 1.734; P = .023), whereas brain metastasis had a worse OS (HR 2.045; P = .028) but not CSS (Zhou et al). These findings highlight the importance of getting a better understanding of mMBC disease biology and the opportunity to tailor treatment approaches for this population of patients.
 

Additional References
 

1. Waks AG, Desai NV, Li T, et al. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022;8:63. Doi: 10.1038/s41523-022-00429-7
2. Park YH, Kim TY, Kim GM, et al; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019;20(12):1750-1759. Doi: 10.1016/S1470-2045(19)30565-0
3. Lefrère H, Lenaerts L, Borges VF, et al. Postpartum breast cancer: mechanisms underlying its worse prognosis, treatment implications, and fertility preservation. Int J Gynecol Cancer. 2021;31:412-422. Doi: 10.1136/ijgc-2020-002072
4. Xie J, Ying YY, Xu B, Li Y, Zhang X, Li C. Metastasis pattern and prognosis of male breast cancer patients in US: a population-based study from SEER database. Ther Adv Med Oncol. 2019;11:1758835919889003. Doi: 10.1177/1758835919889003

A subset of patients with HR+ metastatic breast cancer (mBC) may have primary resistance to endocrine therapy (ET), and the majority will develop progressive disease and secondary resistance at some point during their treatment course. The phase 3 PEARL trial randomly assigned 601 postmenopausal patients with HR+/HER2- mBC that was resistant to prior aromatase inhibitor therapy to capecitabine or palbociclib + ET (with exemestane or fulvestrant). There was no significant difference in OS between the palbociclib + ET and capecitabine arms in both the wild-type–ESR1 population (median OS 37.2 vs 34.8 months; adjusted HR 1.06; P = .683) and overall population (median OS 32.6 vs 30.9 months, adjusted HR 1.00; P = .995) (Martin et al). The randomized phase 2 Young-PEARL trial demonstrated a progression-free survival (PFS) benefit with palbociclib + exemestane + leuprolide vs capecitabine among 189 premenopausal women with HR+/HER2- mBC and relapse or progression on prior tamoxifen therapy (median PFS 20.1 vs 14.4 months; HR 0.659; P = .0235).² In this study, half of the patients were treatment-naive in the metastatic setting and had no prior aromatase inhibitor exposure. Considering the similar survival outcomes seen in PEARL in postmenopausal patients, the choice of therapy should include consideration of other variables, such as side effects, comorbidities, and OS results, which will be further informative in the premenopausal population.
 

Poorer outcomes associated with breast cancer in younger women (< 45 years of age) are driven by multiple factors, including delayed diagnosis, more aggressive biologic subtypes, and advanced stage at presentation. Survival outcomes for breast cancer diagnosed and treated during pregnancy are similar to nonpregnant patients. Postpartum breast cancer (PPBC) is a distinct entity, defined as breast cancer that is diagnosed within the first 5 years after childbirth, and is more likely to have inferior outcomes. A pooled data set from the Colorado Young Women Breast cohort and the Breast Cancer Health Disparities study (n = 2519 cases) showed that among women diagnosed at < 45 years, those who were nulliparous had better OS vs those with PPBC (HR 0.61), with a more prominent effect among stage I breast cancers (HR 0.30) and in very young women diagnosed at ≤ 35 years (HR 0.44) (Shagisultanova et al). At 15 years of follow-up, among very young women diagnosed at ≤ 35 years, those with PPBC had an OS of 63% compared with 71% for nulliparous women and 67% for women who had given birth more than 5 years ago. There are various factors that likely contribute to poorer outcomes seen with PPBC, including mammary gland involution and a lactation effect. Research efforts focused on aspects, such as the tumor immune microenvironment in the postpartum state, lactation studies, and perhaps identification of a postpartum signature, will enhance our understanding with the goal to optimize outcomes for young women with PPBC.^[3]
 

The treatment of male breast cancer in the advanced or metastatic setting is largely extrapolated from female studies. Registry data have shown differences in clinicopathologic characteristics between metastatic male breast cancer (mMBC) and metastatic female breast cancer (mFBC). For example, there is a higher proportion of simultaneous lung and bone involvement and a lower proportion of HER2+/HR- triple-negative subtypes, and simultaneous bone and liver metastasis in mMBC vs mFBC.⁴ An analysis including 207 male patients with breast cancer with bone metastases in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 3-year OS and cancer-specific survival (CSS) rates of 36.7% and 39.5%, respectively. Inferior OS and CSS were associated with age > 60 years (for OS: HR 1.671; P = .014; for CSS: HR 1.806; P = .009), triple-negative subtype (for OS: HR 3.029, P = .003; for CSS: HR 3.025, P = .004), and lack of surgery (for OS: HR 1.746; P = .012; for CSS: HR 1.734; P = .023), whereas brain metastasis had a worse OS (HR 2.045; P = .028) but not CSS (Zhou et al). These findings highlight the importance of getting a better understanding of mMBC disease biology and the opportunity to tailor treatment approaches for this population of patients.
 

Additional References
 

1. Waks AG, Desai NV, Li T, et al. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022;8:63. Doi: 10.1038/s41523-022-00429-7
2. Park YH, Kim TY, Kim GM, et al; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019;20(12):1750-1759. Doi: 10.1016/S1470-2045(19)30565-0
3. Lefrère H, Lenaerts L, Borges VF, et al. Postpartum breast cancer: mechanisms underlying its worse prognosis, treatment implications, and fertility preservation. Int J Gynecol Cancer. 2021;31:412-422. Doi: 10.1136/ijgc-2020-002072
4. Xie J, Ying YY, Xu B, Li Y, Zhang X, Li C. Metastasis pattern and prognosis of male breast cancer patients in US: a population-based study from SEER database. Ther Adv Med Oncol. 2019;11:1758835919889003. Doi: 10.1177/1758835919889003

A subset of patients with HR+ metastatic breast cancer (mBC) may have primary resistance to endocrine therapy (ET), and the majority will develop progressive disease and secondary resistance at some point during their treatment course. The phase 3 PEARL trial randomly assigned 601 postmenopausal patients with HR+/HER2- mBC that was resistant to prior aromatase inhibitor therapy to capecitabine or palbociclib + ET (with exemestane or fulvestrant). There was no significant difference in OS between the palbociclib + ET and capecitabine arms in both the wild-type–ESR1 population (median OS 37.2 vs 34.8 months; adjusted HR 1.06; P = .683) and overall population (median OS 32.6 vs 30.9 months, adjusted HR 1.00; P = .995) (Martin et al). The randomized phase 2 Young-PEARL trial demonstrated a progression-free survival (PFS) benefit with palbociclib + exemestane + leuprolide vs capecitabine among 189 premenopausal women with HR+/HER2- mBC and relapse or progression on prior tamoxifen therapy (median PFS 20.1 vs 14.4 months; HR 0.659; P = .0235).² In this study, half of the patients were treatment-naive in the metastatic setting and had no prior aromatase inhibitor exposure. Considering the similar survival outcomes seen in PEARL in postmenopausal patients, the choice of therapy should include consideration of other variables, such as side effects, comorbidities, and OS results, which will be further informative in the premenopausal population.
 

Poorer outcomes associated with breast cancer in younger women (< 45 years of age) are driven by multiple factors, including delayed diagnosis, more aggressive biologic subtypes, and advanced stage at presentation. Survival outcomes for breast cancer diagnosed and treated during pregnancy are similar to nonpregnant patients. Postpartum breast cancer (PPBC) is a distinct entity, defined as breast cancer that is diagnosed within the first 5 years after childbirth, and is more likely to have inferior outcomes. A pooled data set from the Colorado Young Women Breast cohort and the Breast Cancer Health Disparities study (n = 2519 cases) showed that among women diagnosed at < 45 years, those who were nulliparous had better OS vs those with PPBC (HR 0.61), with a more prominent effect among stage I breast cancers (HR 0.30) and in very young women diagnosed at ≤ 35 years (HR 0.44) (Shagisultanova et al). At 15 years of follow-up, among very young women diagnosed at ≤ 35 years, those with PPBC had an OS of 63% compared with 71% for nulliparous women and 67% for women who had given birth more than 5 years ago. There are various factors that likely contribute to poorer outcomes seen with PPBC, including mammary gland involution and a lactation effect. Research efforts focused on aspects, such as the tumor immune microenvironment in the postpartum state, lactation studies, and perhaps identification of a postpartum signature, will enhance our understanding with the goal to optimize outcomes for young women with PPBC.^[3]
 

The treatment of male breast cancer in the advanced or metastatic setting is largely extrapolated from female studies. Registry data have shown differences in clinicopathologic characteristics between metastatic male breast cancer (mMBC) and metastatic female breast cancer (mFBC). For example, there is a higher proportion of simultaneous lung and bone involvement and a lower proportion of HER2+/HR- triple-negative subtypes, and simultaneous bone and liver metastasis in mMBC vs mFBC.⁴ An analysis including 207 male patients with breast cancer with bone metastases in the Surveillance, Epidemiology, and End Results (SEER) database demonstrated 3-year OS and cancer-specific survival (CSS) rates of 36.7% and 39.5%, respectively. Inferior OS and CSS were associated with age > 60 years (for OS: HR 1.671; P = .014; for CSS: HR 1.806; P = .009), triple-negative subtype (for OS: HR 3.029, P = .003; for CSS: HR 3.025, P = .004), and lack of surgery (for OS: HR 1.746; P = .012; for CSS: HR 1.734; P = .023), whereas brain metastasis had a worse OS (HR 2.045; P = .028) but not CSS (Zhou et al). These findings highlight the importance of getting a better understanding of mMBC disease biology and the opportunity to tailor treatment approaches for this population of patients.
 

Additional References
 

1. Waks AG, Desai NV, Li T, et al. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022;8:63. Doi: 10.1038/s41523-022-00429-7
2. Park YH, Kim TY, Kim GM, et al; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019;20(12):1750-1759. Doi: 10.1016/S1470-2045(19)30565-0
3. Lefrère H, Lenaerts L, Borges VF, et al. Postpartum breast cancer: mechanisms underlying its worse prognosis, treatment implications, and fertility preservation. Int J Gynecol Cancer. 2021;31:412-422. Doi: 10.1136/ijgc-2020-002072
4. Xie J, Ying YY, Xu B, Li Y, Zhang X, Li C. Metastasis pattern and prognosis of male breast cancer patients in US: a population-based study from SEER database. Ther Adv Med Oncol. 2019;11:1758835919889003. Doi: 10.1177/1758835919889003

Clinicians everywhere are excited to have more options, but they are also reeling from trying to keep up with the enormous amount of data. We are fortunate to have a lot of information for these therapies published in the past month, which provides important insight into how to best use them.

Let's start with some new data on dupilumab, which has emerged as a first-line systemic therapy for moderate to severe AD in the US. Patients who were enrolled in the phase 1-3 randomized clinical trials for dupilumab were allowed to enroll in a long-term open-label extension study where they received 300 mg dupilumab weekly. Beck and colleagues published the interim analysis of the ongoing international, multicenter, long-term extension study of 2677 adults with up to 4 years of dupilumab exposure. They found no major increases in adverse event rates, with high durable efficacy and high rates of drug persistence over time. It is important to note that this was an open-label study without a control group — that is, patients knew exactly what treatment they were receiving. In addition, the analysis presented efficacy among those patients who remained in the study over time, which may not adequately account for loss of efficacy over time in patients who dropped out of the study. Nevertheless, the results suggest that dupilumab can be a good long-term treatment option for patients with chronic AD, with no new major safety concerns.

There is now a large body of evidence generated by phase 4 studies showing the real-world effectiveness of dupilumab. Stingeni and colleagues published the results of a prospective study of 139 adolescents (aged 12-17 years) with moderate-to-severe AD who received dupilumab for 16 weeks. They found significant improvement in AD signs and quality of life overall and across different clinical phenotypes of AD, with robust endpoints achieved most in the diffuse eczema subtype. Despite the previously demonstrated heterogeneity of AD,^1,2 these results suggest that dupilumab can be effective across a variety of patient subtypes.

The JAK inhibitors are new additions to our therapeutic armamentarium for AD. Given how new they are to dermatology, we are always craving more data to inform clinical decision-making. Several recent studies provide additional insights into how we can use the JAK inhibitors in clinical practice.

One major question is how well they work in patients in whom dupilumab previously failed. Shi and colleagues published the results of an interesting and clinically relevant phase 3 study (JADE EXTEND), which included 203 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg or 100 mg once-daily abrocitinib after previously receiving dupilumab for 14 weeks in the JADE COMPARE study. They found that at week 12, the majority of dupilumab nonresponders had high Eczema Area and Severity Index (EASI-75) responses with both doses of abrocitinib. Patients who previously had a good clinical response with dupilumab had even higher treatment responses on abrocitinib than those who were dupilumab nonresponders. These data provide important information to support the use of abrocitinib, and perhaps by extension other JAK inhibitors, in patients who previously had inadequate response to dupilumab.

Another major question is how to differentiate the JAK inhibitors from biologics in AD. One consideration is that patients taking JAK inhibitors may achieve more robust clinical responses compared with those on biologics. Stander and colleagues performed a post hoc analysis of pooled phase 2B/3 studies of abrocitinib (942 patients). They found that, at week 12, a higher proportion of patients receiving 200 mg and 100 mg abrocitinib achieved more robust endpoints, such as EASI-90 and EASI-100 scores, compared with placebo recipients. Of note, these data did not include any comparison data with dupilumab. However, on the basis of cross-study comparison, it would seem that abrocitinib, particularly at the higher 200 mg dose, may lead to more robust clinical responses than dupilumab. However, it is very important to acknowledge that this study focused on 12-week data and maximal efficacy with dupilumab may take longer to achieve.

Additional References

1.         Chovatiya R, Silverberg JI. The heterogeneity of atopic dermatitis. J Drugs Dermatol. 2022;21(2):172-176. Doi:  10.36849/JDD.6408

2.         Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Amer Acad Dermatol. 2019;80(2):390-401. Doi: 10.1016/j.jaad.2018.09.035

Clinicians everywhere are excited to have more options, but they are also reeling from trying to keep up with the enormous amount of data. We are fortunate to have a lot of information for these therapies published in the past month, which provides important insight into how to best use them.

Let's start with some new data on dupilumab, which has emerged as a first-line systemic therapy for moderate to severe AD in the US. Patients who were enrolled in the phase 1-3 randomized clinical trials for dupilumab were allowed to enroll in a long-term open-label extension study where they received 300 mg dupilumab weekly. Beck and colleagues published the interim analysis of the ongoing international, multicenter, long-term extension study of 2677 adults with up to 4 years of dupilumab exposure. They found no major increases in adverse event rates, with high durable efficacy and high rates of drug persistence over time. It is important to note that this was an open-label study without a control group — that is, patients knew exactly what treatment they were receiving. In addition, the analysis presented efficacy among those patients who remained in the study over time, which may not adequately account for loss of efficacy over time in patients who dropped out of the study. Nevertheless, the results suggest that dupilumab can be a good long-term treatment option for patients with chronic AD, with no new major safety concerns.

There is now a large body of evidence generated by phase 4 studies showing the real-world effectiveness of dupilumab. Stingeni and colleagues published the results of a prospective study of 139 adolescents (aged 12-17 years) with moderate-to-severe AD who received dupilumab for 16 weeks. They found significant improvement in AD signs and quality of life overall and across different clinical phenotypes of AD, with robust endpoints achieved most in the diffuse eczema subtype. Despite the previously demonstrated heterogeneity of AD,^1,2 these results suggest that dupilumab can be effective across a variety of patient subtypes.

The JAK inhibitors are new additions to our therapeutic armamentarium for AD. Given how new they are to dermatology, we are always craving more data to inform clinical decision-making. Several recent studies provide additional insights into how we can use the JAK inhibitors in clinical practice.

One major question is how well they work in patients in whom dupilumab previously failed. Shi and colleagues published the results of an interesting and clinically relevant phase 3 study (JADE EXTEND), which included 203 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg or 100 mg once-daily abrocitinib after previously receiving dupilumab for 14 weeks in the JADE COMPARE study. They found that at week 12, the majority of dupilumab nonresponders had high Eczema Area and Severity Index (EASI-75) responses with both doses of abrocitinib. Patients who previously had a good clinical response with dupilumab had even higher treatment responses on abrocitinib than those who were dupilumab nonresponders. These data provide important information to support the use of abrocitinib, and perhaps by extension other JAK inhibitors, in patients who previously had inadequate response to dupilumab.

Another major question is how to differentiate the JAK inhibitors from biologics in AD. One consideration is that patients taking JAK inhibitors may achieve more robust clinical responses compared with those on biologics. Stander and colleagues performed a post hoc analysis of pooled phase 2B/3 studies of abrocitinib (942 patients). They found that, at week 12, a higher proportion of patients receiving 200 mg and 100 mg abrocitinib achieved more robust endpoints, such as EASI-90 and EASI-100 scores, compared with placebo recipients. Of note, these data did not include any comparison data with dupilumab. However, on the basis of cross-study comparison, it would seem that abrocitinib, particularly at the higher 200 mg dose, may lead to more robust clinical responses than dupilumab. However, it is very important to acknowledge that this study focused on 12-week data and maximal efficacy with dupilumab may take longer to achieve.

Additional References

1.         Chovatiya R, Silverberg JI. The heterogeneity of atopic dermatitis. J Drugs Dermatol. 2022;21(2):172-176. Doi:  10.36849/JDD.6408

2.         Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Amer Acad Dermatol. 2019;80(2):390-401. Doi: 10.1016/j.jaad.2018.09.035

Clinicians everywhere are excited to have more options, but they are also reeling from trying to keep up with the enormous amount of data. We are fortunate to have a lot of information for these therapies published in the past month, which provides important insight into how to best use them.

Let's start with some new data on dupilumab, which has emerged as a first-line systemic therapy for moderate to severe AD in the US. Patients who were enrolled in the phase 1-3 randomized clinical trials for dupilumab were allowed to enroll in a long-term open-label extension study where they received 300 mg dupilumab weekly. Beck and colleagues published the interim analysis of the ongoing international, multicenter, long-term extension study of 2677 adults with up to 4 years of dupilumab exposure. They found no major increases in adverse event rates, with high durable efficacy and high rates of drug persistence over time. It is important to note that this was an open-label study without a control group — that is, patients knew exactly what treatment they were receiving. In addition, the analysis presented efficacy among those patients who remained in the study over time, which may not adequately account for loss of efficacy over time in patients who dropped out of the study. Nevertheless, the results suggest that dupilumab can be a good long-term treatment option for patients with chronic AD, with no new major safety concerns.

There is now a large body of evidence generated by phase 4 studies showing the real-world effectiveness of dupilumab. Stingeni and colleagues published the results of a prospective study of 139 adolescents (aged 12-17 years) with moderate-to-severe AD who received dupilumab for 16 weeks. They found significant improvement in AD signs and quality of life overall and across different clinical phenotypes of AD, with robust endpoints achieved most in the diffuse eczema subtype. Despite the previously demonstrated heterogeneity of AD,^1,2 these results suggest that dupilumab can be effective across a variety of patient subtypes.

The JAK inhibitors are new additions to our therapeutic armamentarium for AD. Given how new they are to dermatology, we are always craving more data to inform clinical decision-making. Several recent studies provide additional insights into how we can use the JAK inhibitors in clinical practice.

One major question is how well they work in patients in whom dupilumab previously failed. Shi and colleagues published the results of an interesting and clinically relevant phase 3 study (JADE EXTEND), which included 203 patients with moderate-to-severe AD who were randomly assigned to receive 200 mg or 100 mg once-daily abrocitinib after previously receiving dupilumab for 14 weeks in the JADE COMPARE study. They found that at week 12, the majority of dupilumab nonresponders had high Eczema Area and Severity Index (EASI-75) responses with both doses of abrocitinib. Patients who previously had a good clinical response with dupilumab had even higher treatment responses on abrocitinib than those who were dupilumab nonresponders. These data provide important information to support the use of abrocitinib, and perhaps by extension other JAK inhibitors, in patients who previously had inadequate response to dupilumab.

Another major question is how to differentiate the JAK inhibitors from biologics in AD. One consideration is that patients taking JAK inhibitors may achieve more robust clinical responses compared with those on biologics. Stander and colleagues performed a post hoc analysis of pooled phase 2B/3 studies of abrocitinib (942 patients). They found that, at week 12, a higher proportion of patients receiving 200 mg and 100 mg abrocitinib achieved more robust endpoints, such as EASI-90 and EASI-100 scores, compared with placebo recipients. Of note, these data did not include any comparison data with dupilumab. However, on the basis of cross-study comparison, it would seem that abrocitinib, particularly at the higher 200 mg dose, may lead to more robust clinical responses than dupilumab. However, it is very important to acknowledge that this study focused on 12-week data and maximal efficacy with dupilumab may take longer to achieve.

Additional References

1.         Chovatiya R, Silverberg JI. The heterogeneity of atopic dermatitis. J Drugs Dermatol. 2022;21(2):172-176. Doi:  10.36849/JDD.6408

2.         Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J Amer Acad Dermatol. 2019;80(2):390-401. Doi: 10.1016/j.jaad.2018.09.035

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

The negative consequences of structural racism on mental health, and opportunities for change, are the focus of a special issue of the American Journal of Psychiatry, released to coincide with the annual meeting of the American Psychiatric Association.

The hope is this special issue will “motivate clinicians, educators, and researchers to take actions that will make a difference,” Ned H. Kalin, MD, AJP editor-in-chief, wrotes in an editor’s note. 

“We cannot overestimate the impact of structural racism from the standpoint of its consequences related to mental health issues and mental health care,” Dr. Kalin said during an APA press briefing.

“This is one of our highest priorities, if not our highest priority,” he noted. The journal is the “voice of American and international psychiatry” and is a “great vehicle” for moving the field forward, he added.

Articles in the issue highlight “new directions to understand and eliminate mental health disparities [through a] multidimensional lens,” wrote Crystal L. Barksdale, PhD, health scientist administrator and program director with the National Institute on Minority Health and Health Disparities. Dr. Barksdale was guest editor for the issue.
 

A new agenda for change

In one article, Margarita Alegría, PhD, chief of the disparities research unit at Massachusetts General Hospital, Boston, and colleagues, wrote that the Biden Administration’s new budget offers the opportunity to redesign mental health research and service delivery in marginalized communities.

Given the rising mental health crisis in the U.S., the FY22 budget includes $1.6 billion for the community mental health services block grant program, which is more than double the money allocated in FY21.

Dr. Alegría and colleagues describe several interventions that have “sound evidence” of improving mental health or related outcomes among people of color in the U.S. within 5 years – by addressing social determinants of health.

They include universal school meal programs, community-based interventions delivered by paraprofessionals in after-school recreational programs, individual placement and support for employment, mental health literacy programs, senior centers offering health promotion activities, and a chronic disease self-management program.

Dr. Alegría noted that reducing structural racism and mental health disparities requires multilevel structural solutions and action by multiple stakeholders. In essence, “it takes a village,” she said.
 

A national conversation

Another article highlighted at the press briefing focuses on structural racism as it relates to youth suicide prevention.

Studies have shown the risk for suicide is higher earlier in life for youth of color. Suicide rates peak in adolescence and young adulthood for youth of color; for White populations, the peak happens in middle age and later life, noted lead author Kiara Alvarez, PhD, research scientist with Mass General’s disparities research unit.

However, there are well documented mental health service disparities where youth of color experiencing suicidal thoughts and behaviors have lower rates of access to needed services. They also have delays in access compared with their White peers, Dr. Alvarez said.

The authors propose a framework to address structural racism and mental health disparities as it relates to youth suicide prevention, with a focus on systems that are “preventive, rather than reactive; restorative, rather than punitive; and community-driven, rather than externally imposed.

“Ultimately, only structural solutions can dismantle structural racism,” they wrote.

The special issue of AJP aligns with the theme of this year’s APA meeting, which is the social determinants of mental health.

“Mental health has clearly become part of the national conversation. This has given us the opportunity to discuss how factors outside of the office and hospitals can impact the lives of many with mental illness and substance use disorder,” APA President Vivian B. Pender, MD, said during a preconference press briefing. 

“These factors may include where you live, the air you breathe, how you’re educated, exposure to violence, and the impact of racism. These social determinants have become especially relevant to good mental health,” Dr. Pender said.

The research was supported by grants from the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, the National Institute of Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Child Health and Human Development. Dr. Kalin, Dr. Barksdale, Dr. Alegría, Dr. Alvarez, and Dr. Pender have disclosed no relevant financial relationships.

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

The negative consequences of structural racism on mental health, and opportunities for change, are the focus of a special issue of the American Journal of Psychiatry, released to coincide with the annual meeting of the American Psychiatric Association.

The hope is this special issue will “motivate clinicians, educators, and researchers to take actions that will make a difference,” Ned H. Kalin, MD, AJP editor-in-chief, wrotes in an editor’s note. 

“We cannot overestimate the impact of structural racism from the standpoint of its consequences related to mental health issues and mental health care,” Dr. Kalin said during an APA press briefing.

“This is one of our highest priorities, if not our highest priority,” he noted. The journal is the “voice of American and international psychiatry” and is a “great vehicle” for moving the field forward, he added.

Articles in the issue highlight “new directions to understand and eliminate mental health disparities [through a] multidimensional lens,” wrote Crystal L. Barksdale, PhD, health scientist administrator and program director with the National Institute on Minority Health and Health Disparities. Dr. Barksdale was guest editor for the issue.
 

A new agenda for change

In one article, Margarita Alegría, PhD, chief of the disparities research unit at Massachusetts General Hospital, Boston, and colleagues, wrote that the Biden Administration’s new budget offers the opportunity to redesign mental health research and service delivery in marginalized communities.

Given the rising mental health crisis in the U.S., the FY22 budget includes $1.6 billion for the community mental health services block grant program, which is more than double the money allocated in FY21.

Dr. Alegría and colleagues describe several interventions that have “sound evidence” of improving mental health or related outcomes among people of color in the U.S. within 5 years – by addressing social determinants of health.

They include universal school meal programs, community-based interventions delivered by paraprofessionals in after-school recreational programs, individual placement and support for employment, mental health literacy programs, senior centers offering health promotion activities, and a chronic disease self-management program.

Dr. Alegría noted that reducing structural racism and mental health disparities requires multilevel structural solutions and action by multiple stakeholders. In essence, “it takes a village,” she said.
 

A national conversation

Another article highlighted at the press briefing focuses on structural racism as it relates to youth suicide prevention.

Studies have shown the risk for suicide is higher earlier in life for youth of color. Suicide rates peak in adolescence and young adulthood for youth of color; for White populations, the peak happens in middle age and later life, noted lead author Kiara Alvarez, PhD, research scientist with Mass General’s disparities research unit.

However, there are well documented mental health service disparities where youth of color experiencing suicidal thoughts and behaviors have lower rates of access to needed services. They also have delays in access compared with their White peers, Dr. Alvarez said.

The authors propose a framework to address structural racism and mental health disparities as it relates to youth suicide prevention, with a focus on systems that are “preventive, rather than reactive; restorative, rather than punitive; and community-driven, rather than externally imposed.

“Ultimately, only structural solutions can dismantle structural racism,” they wrote.

The special issue of AJP aligns with the theme of this year’s APA meeting, which is the social determinants of mental health.

“Mental health has clearly become part of the national conversation. This has given us the opportunity to discuss how factors outside of the office and hospitals can impact the lives of many with mental illness and substance use disorder,” APA President Vivian B. Pender, MD, said during a preconference press briefing. 

“These factors may include where you live, the air you breathe, how you’re educated, exposure to violence, and the impact of racism. These social determinants have become especially relevant to good mental health,” Dr. Pender said.

The research was supported by grants from the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, the National Institute of Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Child Health and Human Development. Dr. Kalin, Dr. Barksdale, Dr. Alegría, Dr. Alvarez, and Dr. Pender have disclosed no relevant financial relationships.

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

The negative consequences of structural racism on mental health, and opportunities for change, are the focus of a special issue of the American Journal of Psychiatry, released to coincide with the annual meeting of the American Psychiatric Association.

The hope is this special issue will “motivate clinicians, educators, and researchers to take actions that will make a difference,” Ned H. Kalin, MD, AJP editor-in-chief, wrotes in an editor’s note. 

“We cannot overestimate the impact of structural racism from the standpoint of its consequences related to mental health issues and mental health care,” Dr. Kalin said during an APA press briefing.

“This is one of our highest priorities, if not our highest priority,” he noted. The journal is the “voice of American and international psychiatry” and is a “great vehicle” for moving the field forward, he added.

Articles in the issue highlight “new directions to understand and eliminate mental health disparities [through a] multidimensional lens,” wrote Crystal L. Barksdale, PhD, health scientist administrator and program director with the National Institute on Minority Health and Health Disparities. Dr. Barksdale was guest editor for the issue.
 

A new agenda for change

In one article, Margarita Alegría, PhD, chief of the disparities research unit at Massachusetts General Hospital, Boston, and colleagues, wrote that the Biden Administration’s new budget offers the opportunity to redesign mental health research and service delivery in marginalized communities.

Given the rising mental health crisis in the U.S., the FY22 budget includes $1.6 billion for the community mental health services block grant program, which is more than double the money allocated in FY21.

Dr. Alegría and colleagues describe several interventions that have “sound evidence” of improving mental health or related outcomes among people of color in the U.S. within 5 years – by addressing social determinants of health.

They include universal school meal programs, community-based interventions delivered by paraprofessionals in after-school recreational programs, individual placement and support for employment, mental health literacy programs, senior centers offering health promotion activities, and a chronic disease self-management program.

Dr. Alegría noted that reducing structural racism and mental health disparities requires multilevel structural solutions and action by multiple stakeholders. In essence, “it takes a village,” she said.
 

A national conversation

Another article highlighted at the press briefing focuses on structural racism as it relates to youth suicide prevention.

Studies have shown the risk for suicide is higher earlier in life for youth of color. Suicide rates peak in adolescence and young adulthood for youth of color; for White populations, the peak happens in middle age and later life, noted lead author Kiara Alvarez, PhD, research scientist with Mass General’s disparities research unit.

However, there are well documented mental health service disparities where youth of color experiencing suicidal thoughts and behaviors have lower rates of access to needed services. They also have delays in access compared with their White peers, Dr. Alvarez said.

The authors propose a framework to address structural racism and mental health disparities as it relates to youth suicide prevention, with a focus on systems that are “preventive, rather than reactive; restorative, rather than punitive; and community-driven, rather than externally imposed.

“Ultimately, only structural solutions can dismantle structural racism,” they wrote.

The special issue of AJP aligns with the theme of this year’s APA meeting, which is the social determinants of mental health.

“Mental health has clearly become part of the national conversation. This has given us the opportunity to discuss how factors outside of the office and hospitals can impact the lives of many with mental illness and substance use disorder,” APA President Vivian B. Pender, MD, said during a preconference press briefing. 

“These factors may include where you live, the air you breathe, how you’re educated, exposure to violence, and the impact of racism. These social determinants have become especially relevant to good mental health,” Dr. Pender said.

The research was supported by grants from the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities, the National Institute of Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, and the National Institute of Child Health and Human Development. Dr. Kalin, Dr. Barksdale, Dr. Alegría, Dr. Alvarez, and Dr. Pender have disclosed no relevant financial relationships.

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

More than 3 million live births occurred in the United States in 2021, the largest increase in the nation’s birth rate since 2014, according to the U.S. Centers for Disease Control and Prevention.

Provisional data showed a 1% uptick in births, to 3.66 million, after 6 years of dropping by approximately 2% per year. The gains were concentrated among birthing people ages 25 and older. Teenage births, on the other hand, are at their lowest level since the 1990s, according to the CDC. The agency reported a record 6% decrease in births for teenagers aged 15 to 19 years between 2020 and 2021. Women ages 20 to 25 years also had a record decrease in births of 4% during that period.

Brady E. Hamilton, PhD, of the CDC’s National Center for Health Statistics, and the lead author of the new report, said the rise in births points to childbearing that was postponed during the pandemic. Data from 2021 showed a 4% drop in the nation’s birth rate between 2019 and 2020.

“The option to forgo birth is not always viable for older women, but you saw a lot of that during the pandemic,” Dr. Hamilton said. “Events happened related to job security and the economy that caused people to wait to have a child.”

Dr. Hamilton said more data are needed to determine the full impact of increased overall birth rates on individuals. The final report, which will be released in July, will delve deeper into the influence increased birth rates had on demographics and preterm births, which Dr. Hamilton and his team found have increased by 4%.

“For those beginning to have children, we see these trends, but it will be interesting to see what happens to younger women in the future,” Dr. Hamilton said. “Once we have the final data for 2021, we will be able to see a more detailed pattern emerge and draw conclusions from that.”

Dr. Hamilton has disclosed no relevant financial relationships.

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

More than 3 million live births occurred in the United States in 2021, the largest increase in the nation’s birth rate since 2014, according to the U.S. Centers for Disease Control and Prevention.

Provisional data showed a 1% uptick in births, to 3.66 million, after 6 years of dropping by approximately 2% per year. The gains were concentrated among birthing people ages 25 and older. Teenage births, on the other hand, are at their lowest level since the 1990s, according to the CDC. The agency reported a record 6% decrease in births for teenagers aged 15 to 19 years between 2020 and 2021. Women ages 20 to 25 years also had a record decrease in births of 4% during that period.

Brady E. Hamilton, PhD, of the CDC’s National Center for Health Statistics, and the lead author of the new report, said the rise in births points to childbearing that was postponed during the pandemic. Data from 2021 showed a 4% drop in the nation’s birth rate between 2019 and 2020.

“The option to forgo birth is not always viable for older women, but you saw a lot of that during the pandemic,” Dr. Hamilton said. “Events happened related to job security and the economy that caused people to wait to have a child.”

Dr. Hamilton said more data are needed to determine the full impact of increased overall birth rates on individuals. The final report, which will be released in July, will delve deeper into the influence increased birth rates had on demographics and preterm births, which Dr. Hamilton and his team found have increased by 4%.

“For those beginning to have children, we see these trends, but it will be interesting to see what happens to younger women in the future,” Dr. Hamilton said. “Once we have the final data for 2021, we will be able to see a more detailed pattern emerge and draw conclusions from that.”

Dr. Hamilton has disclosed no relevant financial relationships.

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

More than 3 million live births occurred in the United States in 2021, the largest increase in the nation’s birth rate since 2014, according to the U.S. Centers for Disease Control and Prevention.

Provisional data showed a 1% uptick in births, to 3.66 million, after 6 years of dropping by approximately 2% per year. The gains were concentrated among birthing people ages 25 and older. Teenage births, on the other hand, are at their lowest level since the 1990s, according to the CDC. The agency reported a record 6% decrease in births for teenagers aged 15 to 19 years between 2020 and 2021. Women ages 20 to 25 years also had a record decrease in births of 4% during that period.

Brady E. Hamilton, PhD, of the CDC’s National Center for Health Statistics, and the lead author of the new report, said the rise in births points to childbearing that was postponed during the pandemic. Data from 2021 showed a 4% drop in the nation’s birth rate between 2019 and 2020.

“The option to forgo birth is not always viable for older women, but you saw a lot of that during the pandemic,” Dr. Hamilton said. “Events happened related to job security and the economy that caused people to wait to have a child.”

Dr. Hamilton said more data are needed to determine the full impact of increased overall birth rates on individuals. The final report, which will be released in July, will delve deeper into the influence increased birth rates had on demographics and preterm births, which Dr. Hamilton and his team found have increased by 4%.

“For those beginning to have children, we see these trends, but it will be interesting to see what happens to younger women in the future,” Dr. Hamilton said. “Once we have the final data for 2021, we will be able to see a more detailed pattern emerge and draw conclusions from that.”

Dr. Hamilton has disclosed no relevant financial relationships.

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

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

The first in-human trials of a no-implant approach to interatrial shunting to alleviate heart failure symptoms have shown a signal that the procedure reduces peak exercise wedge pressure in recipients a month afterward, according to early trial results.

Colin M. Barker, MD, reported 30-day results of 31 patients who had no-implant interatrial shunting for heart failure across three studies, at the Society for Cardiovascular Angiography & Interventions scientific sessions. The studies included patients with HF with preserved and reduced ejection fraction (HFpEF and HFrEF).

“At 30 days, there was a response with a decrease in the wedge pressures both at rest and at peak exercise, and that was consistent through all three of these initial trials,” Dr. Barker said. In all 33 patients who have been treated to date, there were no major adverse cardiac and cerebrovascular or thromboembolic events through 1 month. (Two of the patients weren’t included in the results Dr. Barker presented.)

The three studies he reported on were the Alleviate-HF-1 (n = 15), Alleviate-HF-2 (n = 11) for patients with HFpEF, and Alleviate-HFrEF (n = 5). The average patient age was 67 years, and all were New York Heart Association class II, III, or IV with elevated peak pulmonary capillary wedge pressure (PCWP).

The device that creates the no-implant shunt as “not very exotic, but it is very effective, and what it does is create a very predictable, reproducible atrial septostomy” between the left and right atria. The device obtains “almost a biopsy” that’s 7 mm in diameter. “There’s no hardware or foreign bodies left inside the patient,” said Dr. Barker, director of interventional cardiology at Vanderbilt University in Nashville, Tenn. “There’s a natural healing process at the rims after the radiofrequency ablation has been done.” Femoral access was used.

Study participants were also asked to complete the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at 1 and 3 months across all three studies, and at 6 months in the Alleviate-HF-1 study. “Just as important is how patients feel,” Dr. Barker said. KCCQ overall summary scores increased at each time interval across all three studies.

“Durability has been proven with multiple different imaging modalities,” Dr. Barker added, explaining that CT scans in 10 of 10 shunts demonstrated patency through 12 months, and 15 of 15 at 6 months. He noted that none of the created shunts have closed yet. At 6 months, the average shunt measured 7.5 mm (± 1.1 mm, n = 22), left atrial diameter decreased 2.4 mm (P = .031) in HFpEF patients, and no significant changes were observed in right ventricular fractional area change or right atrial volume index.

None of the septostomies have had to be closed or enlarged to date, Dr. Barker said. “We are creating an atrial septal defect that we have a lot of comfort and experience with closing with other devices if need be, but that hasn’t been an issue,” he said. “As of now, it’s one size, but as you can imagine, one-size-fits-all is not the way this will go, and this does allow for variations in size ultimately.”

Kirk N. Garratt, MD, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del., noted that the approach to unload the left atrium “is novel, but I think is becoming well accepted in the advanced HF population. There remain questions about long-term consequences of an intentional interatrial shunt – what happens to pulmonary flow dynamics and the like – but to date the impact of this approach has been favorable.

“The liabilities that come with an implanted device in the septal space, both in terms of the durability of the shunt and the impact that it would have on the ability to perform other transseptal procedures, is overcome with this approach,” he added. 

Dr. Barker disclosed he is an advisory board member and consultant to Alleviant Medical. Dr. Garratt is an advisory board member for Abbott.
 

“Grandma’s workouts may have made you healthier.” The title and accompanying photo of a pair of well-worn women’s running shoes caught my eye immediately. For whatever reason, we are a family of exercisers. My wife has competed in several triathlons and won two of them. With her I have cycled across the United States. It has not surprised us that all three of our children have run at least one marathon. I have always viewed their continued devotion to an active lifestyle and their healthy bodies as a tribute to the benefits of our attempts at parenting by example. We certainly didn’t coach them, lecture them, or run family boot camps on weekends and school vacations.

I had never really given much thought as to whether their grandparents also may have played any role in their affinity for physical activity until I read that article. Apparently, my mother was a gifted athlete as a young woman. I have seen photos of her playing tennis, skiing, and diving and heard stories, but I never saw her do any of these activities except a single perfect swan dive when I must have been 8 or 9 years old.

Similarly, scrapbooks reveal that my mother-in-law had an active sports life in high school. But we never saw any evidence of her athletic activity save a devotion to a gentle backstroke in the cold Maine waters during the summer. My wife and I and our children never saw these grandmothers do anything more sporting or physically taxing than single-handedly preparing a full Thanksgiving dinner. How could their exercise habits have influenced the health of their grandchildren?

A team of researchers at the Joslin Diabetes Center in Boston found that female mice who were given the opportunity to exercise produced offspring that had lower fat mass, higher bone mineral density, and insulin levels usually associated with a lower risk of type 2 diabetes. And, in a bit of a surprise, the next generation of offspring accrued a similar benefit even though its mothers were not exercising. The role of exercise in the fathers was eliminated by experimental design.

So it appears that the first-generation offspring’s gametes and hence the third generation was being exposed in utero to something generated by the grandmothers’ exercise. It does not appear to be a behavior pattern that is passed on. It may have to do with epigenetics. Searching for this unknown factor is ongoing and broad based.

Obviously, similar studies in humans are not on the drawing board. Our reproductive cycle is significantly longer than the 2 years of the mouse. However, looking at their current data, the researchers feel comfortable encouraging a mother to exercise during pregnancy as long as it is compatible with the particulars of her obstetrical course. It would be unkind and without basis in fact to blame your mother’s or your mother-in-law’s sedentary behavior for your child’s poor metabolic health. However, it is reasonable to point out to women considering pregnancy that, in addition to avoiding alcohol and smoking, a good dose of exercise during pregnancy will benefit their children. You can point out that it may even benefit their grandchildren. And of course, once the baby is born and a mother feels comfortable returning to her exercise regime, she should go for it. Remind her also that parenting by example is still the best way to do it.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

“Grandma’s workouts may have made you healthier.” The title and accompanying photo of a pair of well-worn women’s running shoes caught my eye immediately. For whatever reason, we are a family of exercisers. My wife has competed in several triathlons and won two of them. With her I have cycled across the United States. It has not surprised us that all three of our children have run at least one marathon. I have always viewed their continued devotion to an active lifestyle and their healthy bodies as a tribute to the benefits of our attempts at parenting by example. We certainly didn’t coach them, lecture them, or run family boot camps on weekends and school vacations.

I had never really given much thought as to whether their grandparents also may have played any role in their affinity for physical activity until I read that article. Apparently, my mother was a gifted athlete as a young woman. I have seen photos of her playing tennis, skiing, and diving and heard stories, but I never saw her do any of these activities except a single perfect swan dive when I must have been 8 or 9 years old.

Similarly, scrapbooks reveal that my mother-in-law had an active sports life in high school. But we never saw any evidence of her athletic activity save a devotion to a gentle backstroke in the cold Maine waters during the summer. My wife and I and our children never saw these grandmothers do anything more sporting or physically taxing than single-handedly preparing a full Thanksgiving dinner. How could their exercise habits have influenced the health of their grandchildren?

A team of researchers at the Joslin Diabetes Center in Boston found that female mice who were given the opportunity to exercise produced offspring that had lower fat mass, higher bone mineral density, and insulin levels usually associated with a lower risk of type 2 diabetes. And, in a bit of a surprise, the next generation of offspring accrued a similar benefit even though its mothers were not exercising. The role of exercise in the fathers was eliminated by experimental design.

So it appears that the first-generation offspring’s gametes and hence the third generation was being exposed in utero to something generated by the grandmothers’ exercise. It does not appear to be a behavior pattern that is passed on. It may have to do with epigenetics. Searching for this unknown factor is ongoing and broad based.

Obviously, similar studies in humans are not on the drawing board. Our reproductive cycle is significantly longer than the 2 years of the mouse. However, looking at their current data, the researchers feel comfortable encouraging a mother to exercise during pregnancy as long as it is compatible with the particulars of her obstetrical course. It would be unkind and without basis in fact to blame your mother’s or your mother-in-law’s sedentary behavior for your child’s poor metabolic health. However, it is reasonable to point out to women considering pregnancy that, in addition to avoiding alcohol and smoking, a good dose of exercise during pregnancy will benefit their children. You can point out that it may even benefit their grandchildren. And of course, once the baby is born and a mother feels comfortable returning to her exercise regime, she should go for it. Remind her also that parenting by example is still the best way to do it.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

“Grandma’s workouts may have made you healthier.” The title and accompanying photo of a pair of well-worn women’s running shoes caught my eye immediately. For whatever reason, we are a family of exercisers. My wife has competed in several triathlons and won two of them. With her I have cycled across the United States. It has not surprised us that all three of our children have run at least one marathon. I have always viewed their continued devotion to an active lifestyle and their healthy bodies as a tribute to the benefits of our attempts at parenting by example. We certainly didn’t coach them, lecture them, or run family boot camps on weekends and school vacations.

I had never really given much thought as to whether their grandparents also may have played any role in their affinity for physical activity until I read that article. Apparently, my mother was a gifted athlete as a young woman. I have seen photos of her playing tennis, skiing, and diving and heard stories, but I never saw her do any of these activities except a single perfect swan dive when I must have been 8 or 9 years old.

Similarly, scrapbooks reveal that my mother-in-law had an active sports life in high school. But we never saw any evidence of her athletic activity save a devotion to a gentle backstroke in the cold Maine waters during the summer. My wife and I and our children never saw these grandmothers do anything more sporting or physically taxing than single-handedly preparing a full Thanksgiving dinner. How could their exercise habits have influenced the health of their grandchildren?

A team of researchers at the Joslin Diabetes Center in Boston found that female mice who were given the opportunity to exercise produced offspring that had lower fat mass, higher bone mineral density, and insulin levels usually associated with a lower risk of type 2 diabetes. And, in a bit of a surprise, the next generation of offspring accrued a similar benefit even though its mothers were not exercising. The role of exercise in the fathers was eliminated by experimental design.

So it appears that the first-generation offspring’s gametes and hence the third generation was being exposed in utero to something generated by the grandmothers’ exercise. It does not appear to be a behavior pattern that is passed on. It may have to do with epigenetics. Searching for this unknown factor is ongoing and broad based.

Obviously, similar studies in humans are not on the drawing board. Our reproductive cycle is significantly longer than the 2 years of the mouse. However, looking at their current data, the researchers feel comfortable encouraging a mother to exercise during pregnancy as long as it is compatible with the particulars of her obstetrical course. It would be unkind and without basis in fact to blame your mother’s or your mother-in-law’s sedentary behavior for your child’s poor metabolic health. However, it is reasonable to point out to women considering pregnancy that, in addition to avoiding alcohol and smoking, a good dose of exercise during pregnancy will benefit their children. You can point out that it may even benefit their grandchildren. And of course, once the baby is born and a mother feels comfortable returning to her exercise regime, she should go for it. Remind her also that parenting by example is still the best way to do it.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

New medications such as emicizumab (Hemlibra) are transforming the lives of patients with hemophilia A, and more treatments are in the pipeline.

“It’s an amazing time to be a hemophilia provider,” Alice D. Ma, MD, University of North Carolina at Chapel Hill hematologist and bleeding disorder specialist, said in an interview. “There are real options, and it’s very exciting.”

But the drugs come with quirks that hematologists must understand, hemophilia specialists cautioned, and stubborn insurers pose significant obstacles to appropriate care. Also, new generations of medications in development offer both hope and more questions.

By far, the biggest game changer in hemophilia A is a monoclonal antibody called emicizumab (Hemlibra), first approved by the Food and Drug Administration for hemophilia A patients with factor VIII inhibitors and then in 2018 for those without factor VIII inhibitors.

“It’s just been getting a bigger and bigger slice of market share as patients and parents really buy in to how great that product is,” Dr. Ma said. “I do not have any hemophilia A patients with factor VIII inhibitors who aren’t on it. That’s just kind of a no-brainer, no ifs, ands, or buts.”

About 50%-60% of her noninhibitor patients with hemophilia A take the drug, she said.

According to its manufacturer, Genentech, the drug “acts like a bridge, bringing factor IXa and factor X together to allow the blood coagulation process to continue without needing to replace factor VIII.”

Since emicizumab is not a blood factor, Dr. Ma said, it doesn’t cross-react with antibodies or inhibitors. “The other thing that is pretty amazing is that it’s given subcutaneously as opposed to intravenously. It’s given under the skin, kind of like an insulin shot, rather than into a vein.”

Prophylaxis treatments did exist for patients with hemophilia A prior to emicizumab, University of North Carolina at Chapel Hill hematologist and blood disorder specialist Nigel S. Key, MB, ChB, said in an interview. But the treatments didn’t stop all bleeding. “We never really kept them under control,” he said, adding that patients needed to get infusions several times a week. “It was cumbersome and took a lot of compliance, a lot of effort to do it.

Thanks to emicizumab, adult patients don’t have to put on tourniquets and stick butterfly needles into their own veins anymore, and parents no longer need to regularly give factor infusions to their children every 2-3 days, Dr. Ma said. Instead, doses may be required just once a week.
 

Not every patient is eager to embrace emicizumab

Emicizumab isn’t necessarily an easy sell. Home-care company pharmacies don’t get reimbursed as much for providing emicizumab, compared with factor infusions, Dr. Ma said, and some of these companies are urging parents to not accept the drug for their kids.

Prior experience can also make people wary. According to Dr. Ma, one of her patients – a 62-year-old man – was reluctant to take factor because he’d gotten infected with HIV from an infusion. “For guys of that certain age, factor was death. It was poison, so you tried really hard not to take it.”

The patient now regrets not taking emicizumab earlier. He told Dr. Ma that his joints “do feel better than when I took factor regularly,” and “he really thinks that it has made his hemophilia recede into the background of his life, which is pretty, pretty nice.”

In fact, Dr. Ma said, he dropped a 7-pound rock on his foot but did not need to take factor or be hospitalized because of bleeding. Instead, he simply “watched a bruise form and then get better.”

As for challenges beyond convincing patients to take emicizumab, Dr. Ma said that insurers can may still refuse to pay for it in noninhibitor patients. “Some of them say you have to fail a regular clotting factor to be able to take Hemlibra,” she said, noting that she finds this viewpoint intolerable.

Hemlibra is remarkably expensive, but treatment of bleeds is also pricey. A 2021 study found that median 6-month hemostatic treatment costs in hemophilia A patients fell from more than $176,000 to barely $128,000 after they started taking the drug.

There’s another hitch. Some hematologists don’t realize that the drug can throw off certain coagulation readings. Dr. Ma recalled that a patient with hemophilia A went to a different healthcare facility for a gall bladder operation, and hematology fellows there failed to adjust his factor VIII level – an extraordinarily high 400%, suggesting high coagulation – to reflect his use of emicizumab.

“My patient bled severely and could have lost his life,” Dr. Ma said.
 

Despite gains, hemophilia B remains hard to treat

The much rarer hemophilia B (the type that affected members of European royal families who descended from Queen Victoria) has proved more difficult to treat than hemophilia A. An estimated 1 in 5,600 males in the United States are born with hemophilia A, compared with 1 in 19,300 males born with hemophilia B. The conditions rarely affect females.

Recombinant factor IX products that replace a missing protein have been improved and can now be given every 7 or 14 days, instead of twice a week, Dr. Key said. As for the future, so-called rebalancing therapies are in phase 3 trials and look promising: “Instead of trying to beef up the proclotting proteins, you’re trying to knock down the anticlotting proteins. ‘Rebalancing’ is a good way to think of it.”

These treatments are also agnostic – like Hemlibra – to the presence of inhibitors, he said.

These drugs could be available within a few years, Dr. Key said. “The major concern is always going to be a risk of thrombosis or clotting. Some of that has only become apparent through clinical trials and require a return to the drawing board to redesign the dosing to hit the safe, sweet spot that prevents bleeds but doesn’t cause clots.”

Dr. Ma agreed that clots are a significant risk from rebalancing agents. “I don’t know that I would put a factor IX patient without an inhibitor on a rebalancing therapy, because we already have pretty darn good therapies for them,” she said. However, factor IX patients with inhibitors do need better treatments, “and we’re all looking forward to the next approved drugs there.”
 

Hoopla for gene therapy, with questions, as well

The prospect of gene therapy for hemophilia, meanwhile, continues to draw attention as phase 3 trials continue. Potentially, gene therapy could be given just once to patients with hemophilia A or hemophilia B and provide bleeding control indefinitely, Dr. Ma said.

However, Dr. Key wondered whether gene therapy may be useful in hemophilia A, since emicizumab has worked so well. “I just don’t see the tsunami of patients who are wanting to undergo gene therapy in the first few years. I think there’ll be relatively slow uptake due to a lot of factors, including reimbursement.”

Hematologist Amar H. Kelkar, MD, of Dana-Farber Cancer Institute in Boston, is also skeptical that a groundswell of patients will embrace gene therapy, even if one-time treatment lasts for years. Current treatments are working well for many patients, Dr. Kelkar said in an interview, “and comfort with novel therapies may be slow within the community, especially if the treatment effect is expected to be transient. This is the same community that was hit hard by contaminated blood products during the HIV crisis, so it may be hard to convince a large number of patients to adopt a new type of therapy. There’s also the issue of the projected high upfront cost of gene therapies. Of course, I’d love to be wrong, especially if cost issues for the patients can be mitigated.”

Moving forward, both Dr. Ma and Dr. Key urged hematologists to send their hemophilia patients to Hemophilia Treatment Centers so they can get specialized care. There are about 140 of these federally funded centers around the country, according to the National Hemophilia Foundation. Many are located in children’s hospitals.

Hemophilia treatment now requires a subspecialty degree of knowledge that’s difficult for a hematologist in general practice to master, Dr. Ma said. “If you have a patient with hemophilia, and you’re in private practice for general hematology/oncology, please send them to a Hemophilia Treatment Center for something like a once-a-year check-in to make sure that the patient is getting comprehensive care.”

Dr. Ma discloses relationships with Takeda (research funding and consultation). Dr. Key discloses relationships with BioMarin and Takeda (advisory board), Novo Nordisk (grants review committee), and Uniqure (steering committee). Dr. Kelkar has no disclosures.

New medications such as emicizumab (Hemlibra) are transforming the lives of patients with hemophilia A, and more treatments are in the pipeline.

“It’s an amazing time to be a hemophilia provider,” Alice D. Ma, MD, University of North Carolina at Chapel Hill hematologist and bleeding disorder specialist, said in an interview. “There are real options, and it’s very exciting.”

But the drugs come with quirks that hematologists must understand, hemophilia specialists cautioned, and stubborn insurers pose significant obstacles to appropriate care. Also, new generations of medications in development offer both hope and more questions.

By far, the biggest game changer in hemophilia A is a monoclonal antibody called emicizumab (Hemlibra), first approved by the Food and Drug Administration for hemophilia A patients with factor VIII inhibitors and then in 2018 for those without factor VIII inhibitors.

“It’s just been getting a bigger and bigger slice of market share as patients and parents really buy in to how great that product is,” Dr. Ma said. “I do not have any hemophilia A patients with factor VIII inhibitors who aren’t on it. That’s just kind of a no-brainer, no ifs, ands, or buts.”

About 50%-60% of her noninhibitor patients with hemophilia A take the drug, she said.

According to its manufacturer, Genentech, the drug “acts like a bridge, bringing factor IXa and factor X together to allow the blood coagulation process to continue without needing to replace factor VIII.”

Since emicizumab is not a blood factor, Dr. Ma said, it doesn’t cross-react with antibodies or inhibitors. “The other thing that is pretty amazing is that it’s given subcutaneously as opposed to intravenously. It’s given under the skin, kind of like an insulin shot, rather than into a vein.”

Prophylaxis treatments did exist for patients with hemophilia A prior to emicizumab, University of North Carolina at Chapel Hill hematologist and blood disorder specialist Nigel S. Key, MB, ChB, said in an interview. But the treatments didn’t stop all bleeding. “We never really kept them under control,” he said, adding that patients needed to get infusions several times a week. “It was cumbersome and took a lot of compliance, a lot of effort to do it.

Thanks to emicizumab, adult patients don’t have to put on tourniquets and stick butterfly needles into their own veins anymore, and parents no longer need to regularly give factor infusions to their children every 2-3 days, Dr. Ma said. Instead, doses may be required just once a week.
 

Not every patient is eager to embrace emicizumab

Emicizumab isn’t necessarily an easy sell. Home-care company pharmacies don’t get reimbursed as much for providing emicizumab, compared with factor infusions, Dr. Ma said, and some of these companies are urging parents to not accept the drug for their kids.

Prior experience can also make people wary. According to Dr. Ma, one of her patients – a 62-year-old man – was reluctant to take factor because he’d gotten infected with HIV from an infusion. “For guys of that certain age, factor was death. It was poison, so you tried really hard not to take it.”

The patient now regrets not taking emicizumab earlier. He told Dr. Ma that his joints “do feel better than when I took factor regularly,” and “he really thinks that it has made his hemophilia recede into the background of his life, which is pretty, pretty nice.”

In fact, Dr. Ma said, he dropped a 7-pound rock on his foot but did not need to take factor or be hospitalized because of bleeding. Instead, he simply “watched a bruise form and then get better.”

As for challenges beyond convincing patients to take emicizumab, Dr. Ma said that insurers can may still refuse to pay for it in noninhibitor patients. “Some of them say you have to fail a regular clotting factor to be able to take Hemlibra,” she said, noting that she finds this viewpoint intolerable.

Hemlibra is remarkably expensive, but treatment of bleeds is also pricey. A 2021 study found that median 6-month hemostatic treatment costs in hemophilia A patients fell from more than $176,000 to barely $128,000 after they started taking the drug.

There’s another hitch. Some hematologists don’t realize that the drug can throw off certain coagulation readings. Dr. Ma recalled that a patient with hemophilia A went to a different healthcare facility for a gall bladder operation, and hematology fellows there failed to adjust his factor VIII level – an extraordinarily high 400%, suggesting high coagulation – to reflect his use of emicizumab.

“My patient bled severely and could have lost his life,” Dr. Ma said.
 

Despite gains, hemophilia B remains hard to treat

The much rarer hemophilia B (the type that affected members of European royal families who descended from Queen Victoria) has proved more difficult to treat than hemophilia A. An estimated 1 in 5,600 males in the United States are born with hemophilia A, compared with 1 in 19,300 males born with hemophilia B. The conditions rarely affect females.

Recombinant factor IX products that replace a missing protein have been improved and can now be given every 7 or 14 days, instead of twice a week, Dr. Key said. As for the future, so-called rebalancing therapies are in phase 3 trials and look promising: “Instead of trying to beef up the proclotting proteins, you’re trying to knock down the anticlotting proteins. ‘Rebalancing’ is a good way to think of it.”

These treatments are also agnostic – like Hemlibra – to the presence of inhibitors, he said.

These drugs could be available within a few years, Dr. Key said. “The major concern is always going to be a risk of thrombosis or clotting. Some of that has only become apparent through clinical trials and require a return to the drawing board to redesign the dosing to hit the safe, sweet spot that prevents bleeds but doesn’t cause clots.”

Dr. Ma agreed that clots are a significant risk from rebalancing agents. “I don’t know that I would put a factor IX patient without an inhibitor on a rebalancing therapy, because we already have pretty darn good therapies for them,” she said. However, factor IX patients with inhibitors do need better treatments, “and we’re all looking forward to the next approved drugs there.”
 

Hoopla for gene therapy, with questions, as well

The prospect of gene therapy for hemophilia, meanwhile, continues to draw attention as phase 3 trials continue. Potentially, gene therapy could be given just once to patients with hemophilia A or hemophilia B and provide bleeding control indefinitely, Dr. Ma said.

However, Dr. Key wondered whether gene therapy may be useful in hemophilia A, since emicizumab has worked so well. “I just don’t see the tsunami of patients who are wanting to undergo gene therapy in the first few years. I think there’ll be relatively slow uptake due to a lot of factors, including reimbursement.”

Hematologist Amar H. Kelkar, MD, of Dana-Farber Cancer Institute in Boston, is also skeptical that a groundswell of patients will embrace gene therapy, even if one-time treatment lasts for years. Current treatments are working well for many patients, Dr. Kelkar said in an interview, “and comfort with novel therapies may be slow within the community, especially if the treatment effect is expected to be transient. This is the same community that was hit hard by contaminated blood products during the HIV crisis, so it may be hard to convince a large number of patients to adopt a new type of therapy. There’s also the issue of the projected high upfront cost of gene therapies. Of course, I’d love to be wrong, especially if cost issues for the patients can be mitigated.”

Moving forward, both Dr. Ma and Dr. Key urged hematologists to send their hemophilia patients to Hemophilia Treatment Centers so they can get specialized care. There are about 140 of these federally funded centers around the country, according to the National Hemophilia Foundation. Many are located in children’s hospitals.

Hemophilia treatment now requires a subspecialty degree of knowledge that’s difficult for a hematologist in general practice to master, Dr. Ma said. “If you have a patient with hemophilia, and you’re in private practice for general hematology/oncology, please send them to a Hemophilia Treatment Center for something like a once-a-year check-in to make sure that the patient is getting comprehensive care.”

Dr. Ma discloses relationships with Takeda (research funding and consultation). Dr. Key discloses relationships with BioMarin and Takeda (advisory board), Novo Nordisk (grants review committee), and Uniqure (steering committee). Dr. Kelkar has no disclosures.

New medications such as emicizumab (Hemlibra) are transforming the lives of patients with hemophilia A, and more treatments are in the pipeline.

“It’s an amazing time to be a hemophilia provider,” Alice D. Ma, MD, University of North Carolina at Chapel Hill hematologist and bleeding disorder specialist, said in an interview. “There are real options, and it’s very exciting.”

But the drugs come with quirks that hematologists must understand, hemophilia specialists cautioned, and stubborn insurers pose significant obstacles to appropriate care. Also, new generations of medications in development offer both hope and more questions.

By far, the biggest game changer in hemophilia A is a monoclonal antibody called emicizumab (Hemlibra), first approved by the Food and Drug Administration for hemophilia A patients with factor VIII inhibitors and then in 2018 for those without factor VIII inhibitors.

“It’s just been getting a bigger and bigger slice of market share as patients and parents really buy in to how great that product is,” Dr. Ma said. “I do not have any hemophilia A patients with factor VIII inhibitors who aren’t on it. That’s just kind of a no-brainer, no ifs, ands, or buts.”

About 50%-60% of her noninhibitor patients with hemophilia A take the drug, she said.

According to its manufacturer, Genentech, the drug “acts like a bridge, bringing factor IXa and factor X together to allow the blood coagulation process to continue without needing to replace factor VIII.”

Since emicizumab is not a blood factor, Dr. Ma said, it doesn’t cross-react with antibodies or inhibitors. “The other thing that is pretty amazing is that it’s given subcutaneously as opposed to intravenously. It’s given under the skin, kind of like an insulin shot, rather than into a vein.”

Prophylaxis treatments did exist for patients with hemophilia A prior to emicizumab, University of North Carolina at Chapel Hill hematologist and blood disorder specialist Nigel S. Key, MB, ChB, said in an interview. But the treatments didn’t stop all bleeding. “We never really kept them under control,” he said, adding that patients needed to get infusions several times a week. “It was cumbersome and took a lot of compliance, a lot of effort to do it.

Thanks to emicizumab, adult patients don’t have to put on tourniquets and stick butterfly needles into their own veins anymore, and parents no longer need to regularly give factor infusions to their children every 2-3 days, Dr. Ma said. Instead, doses may be required just once a week.
 

Not every patient is eager to embrace emicizumab

Emicizumab isn’t necessarily an easy sell. Home-care company pharmacies don’t get reimbursed as much for providing emicizumab, compared with factor infusions, Dr. Ma said, and some of these companies are urging parents to not accept the drug for their kids.

Prior experience can also make people wary. According to Dr. Ma, one of her patients – a 62-year-old man – was reluctant to take factor because he’d gotten infected with HIV from an infusion. “For guys of that certain age, factor was death. It was poison, so you tried really hard not to take it.”

The patient now regrets not taking emicizumab earlier. He told Dr. Ma that his joints “do feel better than when I took factor regularly,” and “he really thinks that it has made his hemophilia recede into the background of his life, which is pretty, pretty nice.”

In fact, Dr. Ma said, he dropped a 7-pound rock on his foot but did not need to take factor or be hospitalized because of bleeding. Instead, he simply “watched a bruise form and then get better.”

As for challenges beyond convincing patients to take emicizumab, Dr. Ma said that insurers can may still refuse to pay for it in noninhibitor patients. “Some of them say you have to fail a regular clotting factor to be able to take Hemlibra,” she said, noting that she finds this viewpoint intolerable.

Hemlibra is remarkably expensive, but treatment of bleeds is also pricey. A 2021 study found that median 6-month hemostatic treatment costs in hemophilia A patients fell from more than $176,000 to barely $128,000 after they started taking the drug.

There’s another hitch. Some hematologists don’t realize that the drug can throw off certain coagulation readings. Dr. Ma recalled that a patient with hemophilia A went to a different healthcare facility for a gall bladder operation, and hematology fellows there failed to adjust his factor VIII level – an extraordinarily high 400%, suggesting high coagulation – to reflect his use of emicizumab.

“My patient bled severely and could have lost his life,” Dr. Ma said.
 

Despite gains, hemophilia B remains hard to treat

The much rarer hemophilia B (the type that affected members of European royal families who descended from Queen Victoria) has proved more difficult to treat than hemophilia A. An estimated 1 in 5,600 males in the United States are born with hemophilia A, compared with 1 in 19,300 males born with hemophilia B. The conditions rarely affect females.

Recombinant factor IX products that replace a missing protein have been improved and can now be given every 7 or 14 days, instead of twice a week, Dr. Key said. As for the future, so-called rebalancing therapies are in phase 3 trials and look promising: “Instead of trying to beef up the proclotting proteins, you’re trying to knock down the anticlotting proteins. ‘Rebalancing’ is a good way to think of it.”

These treatments are also agnostic – like Hemlibra – to the presence of inhibitors, he said.

These drugs could be available within a few years, Dr. Key said. “The major concern is always going to be a risk of thrombosis or clotting. Some of that has only become apparent through clinical trials and require a return to the drawing board to redesign the dosing to hit the safe, sweet spot that prevents bleeds but doesn’t cause clots.”

Dr. Ma agreed that clots are a significant risk from rebalancing agents. “I don’t know that I would put a factor IX patient without an inhibitor on a rebalancing therapy, because we already have pretty darn good therapies for them,” she said. However, factor IX patients with inhibitors do need better treatments, “and we’re all looking forward to the next approved drugs there.”
 

Hoopla for gene therapy, with questions, as well

The prospect of gene therapy for hemophilia, meanwhile, continues to draw attention as phase 3 trials continue. Potentially, gene therapy could be given just once to patients with hemophilia A or hemophilia B and provide bleeding control indefinitely, Dr. Ma said.

However, Dr. Key wondered whether gene therapy may be useful in hemophilia A, since emicizumab has worked so well. “I just don’t see the tsunami of patients who are wanting to undergo gene therapy in the first few years. I think there’ll be relatively slow uptake due to a lot of factors, including reimbursement.”

Hematologist Amar H. Kelkar, MD, of Dana-Farber Cancer Institute in Boston, is also skeptical that a groundswell of patients will embrace gene therapy, even if one-time treatment lasts for years. Current treatments are working well for many patients, Dr. Kelkar said in an interview, “and comfort with novel therapies may be slow within the community, especially if the treatment effect is expected to be transient. This is the same community that was hit hard by contaminated blood products during the HIV crisis, so it may be hard to convince a large number of patients to adopt a new type of therapy. There’s also the issue of the projected high upfront cost of gene therapies. Of course, I’d love to be wrong, especially if cost issues for the patients can be mitigated.”

Moving forward, both Dr. Ma and Dr. Key urged hematologists to send their hemophilia patients to Hemophilia Treatment Centers so they can get specialized care. There are about 140 of these federally funded centers around the country, according to the National Hemophilia Foundation. Many are located in children’s hospitals.

Hemophilia treatment now requires a subspecialty degree of knowledge that’s difficult for a hematologist in general practice to master, Dr. Ma said. “If you have a patient with hemophilia, and you’re in private practice for general hematology/oncology, please send them to a Hemophilia Treatment Center for something like a once-a-year check-in to make sure that the patient is getting comprehensive care.”

Dr. Ma discloses relationships with Takeda (research funding and consultation). Dr. Key discloses relationships with BioMarin and Takeda (advisory board), Novo Nordisk (grants review committee), and Uniqure (steering committee). Dr. Kelkar has no disclosures.