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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
New topicals coming for pediatric atopic dermatitis
LAHAINA, HAWAII – Novel topical medications are in the works that will address the longstanding unmet need for a Food and Drug Administration–approved noncorticosteroid topical for use in pediatric atopic dermatitis, Lawrence F. Eichenfield, MD, reported at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
These new agents will be embraced by clinicians for use in delicate skin areas, as well as in the common clinical scenario involving steroid-averse parents, predicted Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital.
First up is crisaborole (Eucrisa), which is approved for atopic dermatitis (AD) in children aged two years and older and has been under review at the Food and Drug Administration for use in infantile AD. (On March 24, several weeks after the meeting, the FDA approved crisaborole down to aged three months for treatment of mild to moderate AD). Agents earlier in the developmental pipeline include two topical Janus kinase (JAK) inhibitors, ruxolitinib and delgocitinib, as well as tapinarof.
Crisaborole: This phosphodiesterase 4 inhibitor is FDA approved down to 2 years of age. In the phase 4, open-label CrisADe CARE 1 study, crisaborole was studied in 137 children ages 3 months to under 24 months. CrisADe CARE 1, presented at the 2019 annual conference of the Pediatric Dermatology Research Alliance (PeDRA), showed close to a 60% reduction from baseline in Eczema Area and Severity Index (EASI) scores after 28 days of twice-daily therapy in the youngsters, 61% of who had moderate AD, the rest mild disease.
Tolerability and safety were reassuring in the phase 4 study. Although about 3% of subjects each experienced application site pain, discomfort, or erythema, the rate of study discontinuation was impressively low at 2.9%, Dr. Eichenfield observed.
Delgocitinib: Japanese investigators have reported positive results in a phase 2 study of delgocitinib ointment in 98 children and adolescents aged 2-15 years, with AD. After 4 weeks of twice-daily treatment, modified EASI scores improved by a mean of 54% with delgocitinib 0.25% and by 62% with 0.5%, compared with less than a 5% improvement with the vehicle control (J Allergy Clin Immunol. 2019 Dec;144[6]:1575-83). The ointment formulation is being developed specifically for the Japanese market.
Studies of an alternative formulation of the JAK inhibitor as a cream rather than ointment, intended for the U.S. and European markets, are in the early stages, conducted by Leo Pharma. Delgocitinib cream, under study in adults and children down to age 2 years with AD, is also under study for chronic hand dermatitis, a program Dr. Eichenfield is enthusiastic about.
“Hand eczema is something you’re going to hear a lot about in the next 2 years. In the U.S., we have no drug approved specifically for hand eczema. And we actually see a lot of hand eczema in pediatric and adolescent patients. I’d say 75%-80% of the ones I see also have atopic dermatitis,” he said.
Ruxolitinib: Incyte, which is developing the topical JAK inhibitor, recently announced positive results in the first of four phase 3 randomized trials, this one conducted in AD patients aged 12 years and older. The efficacy appears to be comparable to that of topical steroids. Studies in younger children are also planned. Ruxolitinib cream is in advanced clinical trials for treatment of vitiligo.
Tapinarof: This topical aryl hydrocarbon receptor agonist downregulates Th17 cytokines, an attribute desirable for treatment of psoriasis. But it also downregulates Th2 cytokines and improves the damaged skin barrier characteristic of AD via upregulation of the filaggrin and involucrin genes in keratinocytes. In a phase 2b, double-blind clinical trial conducted in 247 adults and adolescents with moderate to severe AD, 12 weeks of once-daily tapinarof 1% enabled 51% of patients to achieve a 75% or greater improvement in EASI scores, compared with 18% in controls on vehicle (J Am Acad Dermatol. 2019 Jan;80[1]:89-98.e3).
Dermavant, which is developing the drug, plans to seek an initial indication for treatment of psoriasis, where a phase 3 study is underway, before pursuing regulatory approval in AD.
Dr. Eichenfield disclosed serving as a consultant or investigator for various pharmaceutical companies, including Pfizer, and Dermavant.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
This article was updated 3/27/20.
LAHAINA, HAWAII – Novel topical medications are in the works that will address the longstanding unmet need for a Food and Drug Administration–approved noncorticosteroid topical for use in pediatric atopic dermatitis, Lawrence F. Eichenfield, MD, reported at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
These new agents will be embraced by clinicians for use in delicate skin areas, as well as in the common clinical scenario involving steroid-averse parents, predicted Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital.
First up is crisaborole (Eucrisa), which is approved for atopic dermatitis (AD) in children aged two years and older and has been under review at the Food and Drug Administration for use in infantile AD. (On March 24, several weeks after the meeting, the FDA approved crisaborole down to aged three months for treatment of mild to moderate AD). Agents earlier in the developmental pipeline include two topical Janus kinase (JAK) inhibitors, ruxolitinib and delgocitinib, as well as tapinarof.
Crisaborole: This phosphodiesterase 4 inhibitor is FDA approved down to 2 years of age. In the phase 4, open-label CrisADe CARE 1 study, crisaborole was studied in 137 children ages 3 months to under 24 months. CrisADe CARE 1, presented at the 2019 annual conference of the Pediatric Dermatology Research Alliance (PeDRA), showed close to a 60% reduction from baseline in Eczema Area and Severity Index (EASI) scores after 28 days of twice-daily therapy in the youngsters, 61% of who had moderate AD, the rest mild disease.
Tolerability and safety were reassuring in the phase 4 study. Although about 3% of subjects each experienced application site pain, discomfort, or erythema, the rate of study discontinuation was impressively low at 2.9%, Dr. Eichenfield observed.
Delgocitinib: Japanese investigators have reported positive results in a phase 2 study of delgocitinib ointment in 98 children and adolescents aged 2-15 years, with AD. After 4 weeks of twice-daily treatment, modified EASI scores improved by a mean of 54% with delgocitinib 0.25% and by 62% with 0.5%, compared with less than a 5% improvement with the vehicle control (J Allergy Clin Immunol. 2019 Dec;144[6]:1575-83). The ointment formulation is being developed specifically for the Japanese market.
Studies of an alternative formulation of the JAK inhibitor as a cream rather than ointment, intended for the U.S. and European markets, are in the early stages, conducted by Leo Pharma. Delgocitinib cream, under study in adults and children down to age 2 years with AD, is also under study for chronic hand dermatitis, a program Dr. Eichenfield is enthusiastic about.
“Hand eczema is something you’re going to hear a lot about in the next 2 years. In the U.S., we have no drug approved specifically for hand eczema. And we actually see a lot of hand eczema in pediatric and adolescent patients. I’d say 75%-80% of the ones I see also have atopic dermatitis,” he said.
Ruxolitinib: Incyte, which is developing the topical JAK inhibitor, recently announced positive results in the first of four phase 3 randomized trials, this one conducted in AD patients aged 12 years and older. The efficacy appears to be comparable to that of topical steroids. Studies in younger children are also planned. Ruxolitinib cream is in advanced clinical trials for treatment of vitiligo.
Tapinarof: This topical aryl hydrocarbon receptor agonist downregulates Th17 cytokines, an attribute desirable for treatment of psoriasis. But it also downregulates Th2 cytokines and improves the damaged skin barrier characteristic of AD via upregulation of the filaggrin and involucrin genes in keratinocytes. In a phase 2b, double-blind clinical trial conducted in 247 adults and adolescents with moderate to severe AD, 12 weeks of once-daily tapinarof 1% enabled 51% of patients to achieve a 75% or greater improvement in EASI scores, compared with 18% in controls on vehicle (J Am Acad Dermatol. 2019 Jan;80[1]:89-98.e3).
Dermavant, which is developing the drug, plans to seek an initial indication for treatment of psoriasis, where a phase 3 study is underway, before pursuing regulatory approval in AD.
Dr. Eichenfield disclosed serving as a consultant or investigator for various pharmaceutical companies, including Pfizer, and Dermavant.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
This article was updated 3/27/20.
LAHAINA, HAWAII – Novel topical medications are in the works that will address the longstanding unmet need for a Food and Drug Administration–approved noncorticosteroid topical for use in pediatric atopic dermatitis, Lawrence F. Eichenfield, MD, reported at the SDEF Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
These new agents will be embraced by clinicians for use in delicate skin areas, as well as in the common clinical scenario involving steroid-averse parents, predicted Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital.
First up is crisaborole (Eucrisa), which is approved for atopic dermatitis (AD) in children aged two years and older and has been under review at the Food and Drug Administration for use in infantile AD. (On March 24, several weeks after the meeting, the FDA approved crisaborole down to aged three months for treatment of mild to moderate AD). Agents earlier in the developmental pipeline include two topical Janus kinase (JAK) inhibitors, ruxolitinib and delgocitinib, as well as tapinarof.
Crisaborole: This phosphodiesterase 4 inhibitor is FDA approved down to 2 years of age. In the phase 4, open-label CrisADe CARE 1 study, crisaborole was studied in 137 children ages 3 months to under 24 months. CrisADe CARE 1, presented at the 2019 annual conference of the Pediatric Dermatology Research Alliance (PeDRA), showed close to a 60% reduction from baseline in Eczema Area and Severity Index (EASI) scores after 28 days of twice-daily therapy in the youngsters, 61% of who had moderate AD, the rest mild disease.
Tolerability and safety were reassuring in the phase 4 study. Although about 3% of subjects each experienced application site pain, discomfort, or erythema, the rate of study discontinuation was impressively low at 2.9%, Dr. Eichenfield observed.
Delgocitinib: Japanese investigators have reported positive results in a phase 2 study of delgocitinib ointment in 98 children and adolescents aged 2-15 years, with AD. After 4 weeks of twice-daily treatment, modified EASI scores improved by a mean of 54% with delgocitinib 0.25% and by 62% with 0.5%, compared with less than a 5% improvement with the vehicle control (J Allergy Clin Immunol. 2019 Dec;144[6]:1575-83). The ointment formulation is being developed specifically for the Japanese market.
Studies of an alternative formulation of the JAK inhibitor as a cream rather than ointment, intended for the U.S. and European markets, are in the early stages, conducted by Leo Pharma. Delgocitinib cream, under study in adults and children down to age 2 years with AD, is also under study for chronic hand dermatitis, a program Dr. Eichenfield is enthusiastic about.
“Hand eczema is something you’re going to hear a lot about in the next 2 years. In the U.S., we have no drug approved specifically for hand eczema. And we actually see a lot of hand eczema in pediatric and adolescent patients. I’d say 75%-80% of the ones I see also have atopic dermatitis,” he said.
Ruxolitinib: Incyte, which is developing the topical JAK inhibitor, recently announced positive results in the first of four phase 3 randomized trials, this one conducted in AD patients aged 12 years and older. The efficacy appears to be comparable to that of topical steroids. Studies in younger children are also planned. Ruxolitinib cream is in advanced clinical trials for treatment of vitiligo.
Tapinarof: This topical aryl hydrocarbon receptor agonist downregulates Th17 cytokines, an attribute desirable for treatment of psoriasis. But it also downregulates Th2 cytokines and improves the damaged skin barrier characteristic of AD via upregulation of the filaggrin and involucrin genes in keratinocytes. In a phase 2b, double-blind clinical trial conducted in 247 adults and adolescents with moderate to severe AD, 12 weeks of once-daily tapinarof 1% enabled 51% of patients to achieve a 75% or greater improvement in EASI scores, compared with 18% in controls on vehicle (J Am Acad Dermatol. 2019 Jan;80[1]:89-98.e3).
Dermavant, which is developing the drug, plans to seek an initial indication for treatment of psoriasis, where a phase 3 study is underway, before pursuing regulatory approval in AD.
Dr. Eichenfield disclosed serving as a consultant or investigator for various pharmaceutical companies, including Pfizer, and Dermavant.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
This article was updated 3/27/20.
REPORTING FROM THE SDEF HAWAII DERMATOLOGY SEMINAR
Maternal methadone opioid maintenance therapy may be tied to smaller postnatal head circumference
GRAPEVINE, TEX. – compared with opioid maintenance therapy with buprenorphine, according to a study presented at the Pregnancy Meeting.
Antenatal ultrasound measurements do not differ by treatment, however, the researchers said. A separate study suggests that serial ultrasound examinations of fetal brain and biometry measurements may not be helpful in patients who receive these medications for opioid use disorder.
To examine the effects of methadone and buprenorphine opioid maintenance therapy on prenatal and postnatal growth parameters, Jay Davis, MD, a maternal-fetal medicine fellow at Stony Brook University in New York, and coinvestigators conducted a retrospective cohort study using medical records from an academic center during 2007-2017. They included women with singleton pregnancies receiving opioid maintenance therapy with methadone or buprenorphine. They compared head circumference percentile, abdominal circumference percentile, head circumference/abdominal circumference ratio, and postnatal head circumference percentile between the two groups. The investigators analyzed the data using the Wilcoxon–Mann–Whitney test, chi-square test, and logistic regression.
The researchers studied 282 cases, including 120 patients who received buprenorphine and 162 who received methadone. Patients who received buprenorphine delivered at a later average gestational age (39 weeks vs. 37.8 weeks) and had newborns with greater average birth weights (3,206 g vs. 2,877 g). Compared with patients who received methadone, patients who received buprenorphine were significantly more likely to have a larger postnatal head circumference percentile (39 vs. 30), Dr. Davis and colleagues reported. This difference remained significant after controlling for race, prescriber, gestational age at delivery, and birth weight.
In a separate study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine, Jose M. Perez Yordan, MD, of the University of New Mexico, Albuquerque, and colleagues examined effects of medications for opioid use disorder on fetal brain and body measurements.
They found that maternal medications for opioid use disorder do not have a clinically significant effect on fetal brain and body measurements, compared with controls. “No consistent pattern of decreased fetal growth was identified, since the body measurement affected did not persist with serial ultrasounds,” they said. “Serial ultrasound examinations do not appear to be helpful in patients” who take medications of opioid use disorder, with or without alcohol coexposure, unless other risk factors are present.
To evaluate the effects of medications of opioid use disorder and alcohol coexposure on fetal brain and biometric measurements at the second- and third-trimester ultrasound measurements, the investigators are conducting a prospective study known as ENRICH-1. The study includes healthy controls, patients taking medications of opioid use disorder (that is, buprenorphine or methadone), and patients taking medications of opioid use disorder with alcohol coexposure.
Ultrasound measurements from the second and third trimesters evaluated biparietal diameter, femur length, frontal lobe width and length, front-thalamic distance, and caval-calvarial distance. Univariate and multivariate analyses assessed differences in measurements adjusting for gestational age and other factors.
The present analysis included data from 171 participants, including 56 healthy controls, 75 patients taking medications of opioid use disorder, and 40 patients taking medications of opioid use disorder with alcohol coexposure. There was no consistent pattern of decreased fetal growth. Affected measurements did not persist over time.
The study presented by Dr. Perez Yordan was supported by a National Institute on Alcohol Abuse and Alcoholism grant. The remaining investigators in both studies had no relevant financial disclosures.
SOURCE: Perez Yordan JM et al. Am J Obstet Gynecol. 2020 Jan;222(1):S110, Abstract 149; Davis J et al. Am J Obstet Gynecol. 2020 Jan;222(1):S430, Abstract 678.
GRAPEVINE, TEX. – compared with opioid maintenance therapy with buprenorphine, according to a study presented at the Pregnancy Meeting.
Antenatal ultrasound measurements do not differ by treatment, however, the researchers said. A separate study suggests that serial ultrasound examinations of fetal brain and biometry measurements may not be helpful in patients who receive these medications for opioid use disorder.
To examine the effects of methadone and buprenorphine opioid maintenance therapy on prenatal and postnatal growth parameters, Jay Davis, MD, a maternal-fetal medicine fellow at Stony Brook University in New York, and coinvestigators conducted a retrospective cohort study using medical records from an academic center during 2007-2017. They included women with singleton pregnancies receiving opioid maintenance therapy with methadone or buprenorphine. They compared head circumference percentile, abdominal circumference percentile, head circumference/abdominal circumference ratio, and postnatal head circumference percentile between the two groups. The investigators analyzed the data using the Wilcoxon–Mann–Whitney test, chi-square test, and logistic regression.
The researchers studied 282 cases, including 120 patients who received buprenorphine and 162 who received methadone. Patients who received buprenorphine delivered at a later average gestational age (39 weeks vs. 37.8 weeks) and had newborns with greater average birth weights (3,206 g vs. 2,877 g). Compared with patients who received methadone, patients who received buprenorphine were significantly more likely to have a larger postnatal head circumference percentile (39 vs. 30), Dr. Davis and colleagues reported. This difference remained significant after controlling for race, prescriber, gestational age at delivery, and birth weight.
In a separate study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine, Jose M. Perez Yordan, MD, of the University of New Mexico, Albuquerque, and colleagues examined effects of medications for opioid use disorder on fetal brain and body measurements.
They found that maternal medications for opioid use disorder do not have a clinically significant effect on fetal brain and body measurements, compared with controls. “No consistent pattern of decreased fetal growth was identified, since the body measurement affected did not persist with serial ultrasounds,” they said. “Serial ultrasound examinations do not appear to be helpful in patients” who take medications of opioid use disorder, with or without alcohol coexposure, unless other risk factors are present.
To evaluate the effects of medications of opioid use disorder and alcohol coexposure on fetal brain and biometric measurements at the second- and third-trimester ultrasound measurements, the investigators are conducting a prospective study known as ENRICH-1. The study includes healthy controls, patients taking medications of opioid use disorder (that is, buprenorphine or methadone), and patients taking medications of opioid use disorder with alcohol coexposure.
Ultrasound measurements from the second and third trimesters evaluated biparietal diameter, femur length, frontal lobe width and length, front-thalamic distance, and caval-calvarial distance. Univariate and multivariate analyses assessed differences in measurements adjusting for gestational age and other factors.
The present analysis included data from 171 participants, including 56 healthy controls, 75 patients taking medications of opioid use disorder, and 40 patients taking medications of opioid use disorder with alcohol coexposure. There was no consistent pattern of decreased fetal growth. Affected measurements did not persist over time.
The study presented by Dr. Perez Yordan was supported by a National Institute on Alcohol Abuse and Alcoholism grant. The remaining investigators in both studies had no relevant financial disclosures.
SOURCE: Perez Yordan JM et al. Am J Obstet Gynecol. 2020 Jan;222(1):S110, Abstract 149; Davis J et al. Am J Obstet Gynecol. 2020 Jan;222(1):S430, Abstract 678.
GRAPEVINE, TEX. – compared with opioid maintenance therapy with buprenorphine, according to a study presented at the Pregnancy Meeting.
Antenatal ultrasound measurements do not differ by treatment, however, the researchers said. A separate study suggests that serial ultrasound examinations of fetal brain and biometry measurements may not be helpful in patients who receive these medications for opioid use disorder.
To examine the effects of methadone and buprenorphine opioid maintenance therapy on prenatal and postnatal growth parameters, Jay Davis, MD, a maternal-fetal medicine fellow at Stony Brook University in New York, and coinvestigators conducted a retrospective cohort study using medical records from an academic center during 2007-2017. They included women with singleton pregnancies receiving opioid maintenance therapy with methadone or buprenorphine. They compared head circumference percentile, abdominal circumference percentile, head circumference/abdominal circumference ratio, and postnatal head circumference percentile between the two groups. The investigators analyzed the data using the Wilcoxon–Mann–Whitney test, chi-square test, and logistic regression.
The researchers studied 282 cases, including 120 patients who received buprenorphine and 162 who received methadone. Patients who received buprenorphine delivered at a later average gestational age (39 weeks vs. 37.8 weeks) and had newborns with greater average birth weights (3,206 g vs. 2,877 g). Compared with patients who received methadone, patients who received buprenorphine were significantly more likely to have a larger postnatal head circumference percentile (39 vs. 30), Dr. Davis and colleagues reported. This difference remained significant after controlling for race, prescriber, gestational age at delivery, and birth weight.
In a separate study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine, Jose M. Perez Yordan, MD, of the University of New Mexico, Albuquerque, and colleagues examined effects of medications for opioid use disorder on fetal brain and body measurements.
They found that maternal medications for opioid use disorder do not have a clinically significant effect on fetal brain and body measurements, compared with controls. “No consistent pattern of decreased fetal growth was identified, since the body measurement affected did not persist with serial ultrasounds,” they said. “Serial ultrasound examinations do not appear to be helpful in patients” who take medications of opioid use disorder, with or without alcohol coexposure, unless other risk factors are present.
To evaluate the effects of medications of opioid use disorder and alcohol coexposure on fetal brain and biometric measurements at the second- and third-trimester ultrasound measurements, the investigators are conducting a prospective study known as ENRICH-1. The study includes healthy controls, patients taking medications of opioid use disorder (that is, buprenorphine or methadone), and patients taking medications of opioid use disorder with alcohol coexposure.
Ultrasound measurements from the second and third trimesters evaluated biparietal diameter, femur length, frontal lobe width and length, front-thalamic distance, and caval-calvarial distance. Univariate and multivariate analyses assessed differences in measurements adjusting for gestational age and other factors.
The present analysis included data from 171 participants, including 56 healthy controls, 75 patients taking medications of opioid use disorder, and 40 patients taking medications of opioid use disorder with alcohol coexposure. There was no consistent pattern of decreased fetal growth. Affected measurements did not persist over time.
The study presented by Dr. Perez Yordan was supported by a National Institute on Alcohol Abuse and Alcoholism grant. The remaining investigators in both studies had no relevant financial disclosures.
SOURCE: Perez Yordan JM et al. Am J Obstet Gynecol. 2020 Jan;222(1):S110, Abstract 149; Davis J et al. Am J Obstet Gynecol. 2020 Jan;222(1):S430, Abstract 678.
REPORTING FROM THE PREGNANCY MEETING
Study finds spironolactone doesn’t boost breast cancer recurrence
in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.
Not so, said Mr. Wei, from George Washington University.
He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.
“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.
In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.
In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.
Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.
“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).
Mr. Wei reported having no financial conflicts regarding his unfunded study.
in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.
Not so, said Mr. Wei, from George Washington University.
He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.
“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.
In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.
In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.
Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.
“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).
Mr. Wei reported having no financial conflicts regarding his unfunded study.
in a large retrospective study, Chapman Wei said in a in a virtual meeting held by the George Washington University department of dermatology in Washington. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.
Spironolactone is an aldosterone antagonist and heart failure medication that, because of its peripheral antiandrogen effects, is often used off-label to treat female androgenetic hair loss. Although it has been available for nigh on half a century and has a well-established favorable safety profile, with no indication of carcinogenic effects, little is known about its use in treating alopecia in breast cancer survivors on endocrine therapies, where there has been a theoretic possibility that the drug’s antiandrogen effects could promote breast cancer recurrence.
Not so, said Mr. Wei, from George Washington University.
He presented a retrospective, propensity score–matched, case-control study that used the Humana Insurance database. The initial comparison was between 746 women who went on spironolactone after their breast cancer diagnosis versus 28,400 female breast cancer patients who didn’t take the drug. The primary outcome was recurrent breast cancer within 2 years after diagnosis.
“We chose 2 years because most breast cancer relapses occur within that time,” Mr. Wei explained.
In the initial unadjusted between-group comparison, the breast cancer recurrence rate was 16.5% in the spironolactone group, significantly higher than the 12.8% rate in more than 28,000 controls. However, in a comparison between the spironolactone group and 746 controls extensively propensity score–matched for acne, hypertension, hirsutism, smoking, illicit drug use, heart failure, primary aldosteronism, and other potential confounding variables, there was no significant difference between spironolactone users and controls, with 2-year breast cancer recurrence rates of 16.5% and 15.8%, respectively.
In a multivariate Cox regression analysis, the stand-out finding was that alcohol abuse was independently associated with a 2.3-fold increased risk of breast cancer recurrence.
Mr. Wei noted that these findings confirm those in a recent literature review by investigators at Memorial Sloan Kettering Cancer Center in New York who found no increase in estrogen levels with spironolactone and no heightened risk of female breast cancer while on the drug in three studies totaling 49,298 patients.
“Spironolactone has the potential to be used as a relatively safe systemic treatment option for the management of [endocrine therapy–induced alopecia] in female breast cancer patients and survivors on endocrine therapies who respond poorly to monotherapy with topical minoxidil,” the Sloan Kettering researchers declared (Breast Cancer Res Treat. 2019 Feb;174[1]:15-26).
Mr. Wei reported having no financial conflicts regarding his unfunded study.
Survey explores the role of social media in choosing a dermatologist
Fewer than one-quarter of consumers rely heavily on social media for choosing a dermatologist, results from an online survey suggest.
In a video presentation during a virtual meeting held by the George Washington University department of dermatology, Kamaria Nelson, MD, said that, as of 2019, 79% of Americans have a social media account, with the majority using platforms such as Facebook, Instagram, Twitter, and YouTube. “There’s also a high predominance of social media use in the dermatology field, with many dermatologists assuming that it will improve their personal brands,” said Dr. Nelson, a research fellow in the department of dermatology at George Washington University, Washington. “Some even hire social media managers to monitor online reviews and mitigate any damage. So, although social media is commonly used, it’s unknown if it impacts patient knowledge, access to health care, or provider choice.”
To evaluate how social media influences patients when choosing a dermatologist, she and her colleagues used Survey Monkey to create a 10-item questionnaire that they distributed to 1,481 individuals in the general U.S. population in May 2019. Individuals qualified for the study if they used social media and if they had ever been to a dermatologist. Dr. Nelson reported that 726 individuals (58%) qualified for the survey and 715 completed it, for a response rate of 98%. The researchers used Chi-square tests to compare frequency and importance of social media by visit type, age, gender, and educational level.
When the respondents were stratified by visit type, 43% who saw a dermatologist for cosmetic reasons were more likely to view social media as “extremely important” or “very important,” compared with 15% of patients who saw a dermatologist for medical reasons (P less than .0001).
When stratified by age, about 12% of respondents between the ages of 18 and 44 years considered social media as extremely important when choosing a dermatologist, compared with only 9% of those aged 45-60 years and about 2% of those older than age 60 (P less than .0001).
When stratified by educational level, 30% of respondents with a high school degree or less were more likely to view social media as extremely important or very important when choosing a dermatologist, while 62% of those with more than a high school degree were more likely to view social media as “not at all important” or only “slightly important” (P = .0006).
One of the survey questions was, “When choosing a dermatologist to see, how important is his or her social media site?” Only 9% of respondents said extremely important, 13% said very important, 21% said “moderately important,” 24% said slightly important, and 33% said not at all important. “This left about 22% of respondents who viewed the social media site as extremely important or very important when choosing a dermatologist,” Dr. Nelson said.
Factors deemed important on a dermatologist’s social media profile were patient reviews (68%), years of experience (61%), and the amount of medical information written by the dermatologist (59%).
“There seems to be a low reliance on social media when selecting a dermatologist,” Dr. Nelson concluded. “We also found that cosmetic patients, patients with lower levels of education, and younger patients were more likely to value social media. Therefore, social media may only be useful for targeting specific patient populations. When doing so, medical information written by a provider is most often desired.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Nelson reported having no disclosures.
Fewer than one-quarter of consumers rely heavily on social media for choosing a dermatologist, results from an online survey suggest.
In a video presentation during a virtual meeting held by the George Washington University department of dermatology, Kamaria Nelson, MD, said that, as of 2019, 79% of Americans have a social media account, with the majority using platforms such as Facebook, Instagram, Twitter, and YouTube. “There’s also a high predominance of social media use in the dermatology field, with many dermatologists assuming that it will improve their personal brands,” said Dr. Nelson, a research fellow in the department of dermatology at George Washington University, Washington. “Some even hire social media managers to monitor online reviews and mitigate any damage. So, although social media is commonly used, it’s unknown if it impacts patient knowledge, access to health care, or provider choice.”
To evaluate how social media influences patients when choosing a dermatologist, she and her colleagues used Survey Monkey to create a 10-item questionnaire that they distributed to 1,481 individuals in the general U.S. population in May 2019. Individuals qualified for the study if they used social media and if they had ever been to a dermatologist. Dr. Nelson reported that 726 individuals (58%) qualified for the survey and 715 completed it, for a response rate of 98%. The researchers used Chi-square tests to compare frequency and importance of social media by visit type, age, gender, and educational level.
When the respondents were stratified by visit type, 43% who saw a dermatologist for cosmetic reasons were more likely to view social media as “extremely important” or “very important,” compared with 15% of patients who saw a dermatologist for medical reasons (P less than .0001).
When stratified by age, about 12% of respondents between the ages of 18 and 44 years considered social media as extremely important when choosing a dermatologist, compared with only 9% of those aged 45-60 years and about 2% of those older than age 60 (P less than .0001).
When stratified by educational level, 30% of respondents with a high school degree or less were more likely to view social media as extremely important or very important when choosing a dermatologist, while 62% of those with more than a high school degree were more likely to view social media as “not at all important” or only “slightly important” (P = .0006).
One of the survey questions was, “When choosing a dermatologist to see, how important is his or her social media site?” Only 9% of respondents said extremely important, 13% said very important, 21% said “moderately important,” 24% said slightly important, and 33% said not at all important. “This left about 22% of respondents who viewed the social media site as extremely important or very important when choosing a dermatologist,” Dr. Nelson said.
Factors deemed important on a dermatologist’s social media profile were patient reviews (68%), years of experience (61%), and the amount of medical information written by the dermatologist (59%).
“There seems to be a low reliance on social media when selecting a dermatologist,” Dr. Nelson concluded. “We also found that cosmetic patients, patients with lower levels of education, and younger patients were more likely to value social media. Therefore, social media may only be useful for targeting specific patient populations. When doing so, medical information written by a provider is most often desired.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Nelson reported having no disclosures.
Fewer than one-quarter of consumers rely heavily on social media for choosing a dermatologist, results from an online survey suggest.
In a video presentation during a virtual meeting held by the George Washington University department of dermatology, Kamaria Nelson, MD, said that, as of 2019, 79% of Americans have a social media account, with the majority using platforms such as Facebook, Instagram, Twitter, and YouTube. “There’s also a high predominance of social media use in the dermatology field, with many dermatologists assuming that it will improve their personal brands,” said Dr. Nelson, a research fellow in the department of dermatology at George Washington University, Washington. “Some even hire social media managers to monitor online reviews and mitigate any damage. So, although social media is commonly used, it’s unknown if it impacts patient knowledge, access to health care, or provider choice.”
To evaluate how social media influences patients when choosing a dermatologist, she and her colleagues used Survey Monkey to create a 10-item questionnaire that they distributed to 1,481 individuals in the general U.S. population in May 2019. Individuals qualified for the study if they used social media and if they had ever been to a dermatologist. Dr. Nelson reported that 726 individuals (58%) qualified for the survey and 715 completed it, for a response rate of 98%. The researchers used Chi-square tests to compare frequency and importance of social media by visit type, age, gender, and educational level.
When the respondents were stratified by visit type, 43% who saw a dermatologist for cosmetic reasons were more likely to view social media as “extremely important” or “very important,” compared with 15% of patients who saw a dermatologist for medical reasons (P less than .0001).
When stratified by age, about 12% of respondents between the ages of 18 and 44 years considered social media as extremely important when choosing a dermatologist, compared with only 9% of those aged 45-60 years and about 2% of those older than age 60 (P less than .0001).
When stratified by educational level, 30% of respondents with a high school degree or less were more likely to view social media as extremely important or very important when choosing a dermatologist, while 62% of those with more than a high school degree were more likely to view social media as “not at all important” or only “slightly important” (P = .0006).
One of the survey questions was, “When choosing a dermatologist to see, how important is his or her social media site?” Only 9% of respondents said extremely important, 13% said very important, 21% said “moderately important,” 24% said slightly important, and 33% said not at all important. “This left about 22% of respondents who viewed the social media site as extremely important or very important when choosing a dermatologist,” Dr. Nelson said.
Factors deemed important on a dermatologist’s social media profile were patient reviews (68%), years of experience (61%), and the amount of medical information written by the dermatologist (59%).
“There seems to be a low reliance on social media when selecting a dermatologist,” Dr. Nelson concluded. “We also found that cosmetic patients, patients with lower levels of education, and younger patients were more likely to value social media. Therefore, social media may only be useful for targeting specific patient populations. When doing so, medical information written by a provider is most often desired.”
The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Nelson reported having no disclosures.
Study: Delays filling biologic prescriptions have consequences
Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.
The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.
The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.
The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.
He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”
What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.
The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.
For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m2. Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.
The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.
Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.
The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.
Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.
Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.
One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.
“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”
Dr. Ishmael has no relevant financial relationships to disclose.
SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.
Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.
The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.
The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.
The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.
He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”
What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.
The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.
For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m2. Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.
The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.
Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.
The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.
Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.
Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.
One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.
“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”
Dr. Ishmael has no relevant financial relationships to disclose.
SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.
Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.
The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.
The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.
The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.
He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”
What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.
The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.
For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m2. Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.
The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.
Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.
The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.
Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.
Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.
One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.
“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”
Dr. Ishmael has no relevant financial relationships to disclose.
SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.
REPORTING FROM AAAAI
Intracranial artery stenting shows promising 1-year results
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
REPORTING FROM ISC 2020
Webinar confronts unique issues for the bleeding disorders community facing COVID-19
In a webinar conducted on March 20, Leonard Valentino, MD, president and CEO of the National Hemophilia Foundation (NHF), provided
Overall, the risk of comorbidities is no different in the bleeding disorders population than in the general population, and similar precautions should be maintained, Dr. Valentino stated. He listed some of the at-risk populations as designated by the Centers for Disease Control and Prevention.
In particular, he pointed out that, when the CDC referred to a greater risk of COVID-19 to individuals with bleeding disorders, the organization was referring to patients with HIV and sickle cell disease. The CDC was not referring to patients with other forms of bleeding disorders, such as hemophilia, Dr. Valentino stated.
All individuals should be following CDC and state and federal recommendations with regard to social distancing and hygiene. However, with regard to immunocompromised individuals, “the two populations we [in the bleeding disorders community] have to be concerned about are those in gene therapy clinical trials and those with inhibitors,” said Dr. Valentino.
Patients in a gene therapy clinical trial should exercise additional precautions because the use of steroids, common in these trials. “Steroids are an immunosuppressive drug, and this would increase one’s risk of infection, including COVID-19,” according to Dr. Valentino.
In addition, “I will say, if you have hemophilia and an inhibitor [an antibody to clotting factor treatment], that may alter the immune system, and we don’t know what the implication of that is in terms of coronavirus infection and COVID-19 disease. So people with an inhibitor should take special precautions to limit their exposures.”
Patients with a port should not need to have extra concerns regarding COVID-19, but they should continue to exercise the good hygiene that has always been essential, according to Dr. Valentino.
Dr. Valentino asked: Are patients with a bleeding disorder who become infected with COVID-19 more susceptible to a bleed? “You shouldn’t be more susceptible to bleeding except if you have severe cough, and that cough could result in bleeding to the head,” he answered.
If a patient needs to go to the emergency department for a bleed or possible COVID-19 infection, they should wear a face mask if they are sick to prevent spreading of disease. “This is really the only instance where a face mask may be beneficial” in that it limits other people’s exposure to your infection. It is especially important to call ahead before visiting the doctor or going to the emergency department. “Make sure that they’re aware that you’re coming.”
Of particular concern to patients is the amount of factor product they should have on hand. The current CDC recommendation is a 30-day supply of medicines, but that is misleading, because it refers to general medications, such as high-blood pressure medicine, and not factor products. “The current MASAC [NHF’s Medical and Scientific Advisory Council] recommendation is to have a 14-day supply of factor products available to you,” said Dr. Valentino, “and one should reorder when you have a 1-week supply.”
MASAC has issued a letter on the crisis on the NHF website.
These recommendations should not be exceeded in order to ensure that there is enough factor available to all patients, he added. Hoarding is discouraged, and there are no concerns as yet of factor running out. “We have had conversations with manufacturers and … the supply chain is robust.” The greater concern is with regard to ancillary supplies in the hospital that a hemophilia patient may require during treatment.
Patients and practitioners should consult the COVID-19 pages of both the NHF and Hemophilia Federation of America (HFA) websites. This includes a Health and Wellness update by Dr. Valentino.
With regard to financial issues, he and Sharon Meyers, CEO and president of the HFA, spoke, stating that both NHF and HFA have advocacy for patients seeking to deal with insurance issues or in paying for their products, urging people to go to the organizational websites and to also use their emails: advocate@hemophilia.org and advocacy@hemophiliafed.org.
She also announced that the annual meeting of the HFA was being postponed to Aug. 24-26 at the Hilton Inner Harbor Baltimore, Md.
Dr. Valentino and Ms. Meyers did not provide any disclosure information.
In a webinar conducted on March 20, Leonard Valentino, MD, president and CEO of the National Hemophilia Foundation (NHF), provided
Overall, the risk of comorbidities is no different in the bleeding disorders population than in the general population, and similar precautions should be maintained, Dr. Valentino stated. He listed some of the at-risk populations as designated by the Centers for Disease Control and Prevention.
In particular, he pointed out that, when the CDC referred to a greater risk of COVID-19 to individuals with bleeding disorders, the organization was referring to patients with HIV and sickle cell disease. The CDC was not referring to patients with other forms of bleeding disorders, such as hemophilia, Dr. Valentino stated.
All individuals should be following CDC and state and federal recommendations with regard to social distancing and hygiene. However, with regard to immunocompromised individuals, “the two populations we [in the bleeding disorders community] have to be concerned about are those in gene therapy clinical trials and those with inhibitors,” said Dr. Valentino.
Patients in a gene therapy clinical trial should exercise additional precautions because the use of steroids, common in these trials. “Steroids are an immunosuppressive drug, and this would increase one’s risk of infection, including COVID-19,” according to Dr. Valentino.
In addition, “I will say, if you have hemophilia and an inhibitor [an antibody to clotting factor treatment], that may alter the immune system, and we don’t know what the implication of that is in terms of coronavirus infection and COVID-19 disease. So people with an inhibitor should take special precautions to limit their exposures.”
Patients with a port should not need to have extra concerns regarding COVID-19, but they should continue to exercise the good hygiene that has always been essential, according to Dr. Valentino.
Dr. Valentino asked: Are patients with a bleeding disorder who become infected with COVID-19 more susceptible to a bleed? “You shouldn’t be more susceptible to bleeding except if you have severe cough, and that cough could result in bleeding to the head,” he answered.
If a patient needs to go to the emergency department for a bleed or possible COVID-19 infection, they should wear a face mask if they are sick to prevent spreading of disease. “This is really the only instance where a face mask may be beneficial” in that it limits other people’s exposure to your infection. It is especially important to call ahead before visiting the doctor or going to the emergency department. “Make sure that they’re aware that you’re coming.”
Of particular concern to patients is the amount of factor product they should have on hand. The current CDC recommendation is a 30-day supply of medicines, but that is misleading, because it refers to general medications, such as high-blood pressure medicine, and not factor products. “The current MASAC [NHF’s Medical and Scientific Advisory Council] recommendation is to have a 14-day supply of factor products available to you,” said Dr. Valentino, “and one should reorder when you have a 1-week supply.”
MASAC has issued a letter on the crisis on the NHF website.
These recommendations should not be exceeded in order to ensure that there is enough factor available to all patients, he added. Hoarding is discouraged, and there are no concerns as yet of factor running out. “We have had conversations with manufacturers and … the supply chain is robust.” The greater concern is with regard to ancillary supplies in the hospital that a hemophilia patient may require during treatment.
Patients and practitioners should consult the COVID-19 pages of both the NHF and Hemophilia Federation of America (HFA) websites. This includes a Health and Wellness update by Dr. Valentino.
With regard to financial issues, he and Sharon Meyers, CEO and president of the HFA, spoke, stating that both NHF and HFA have advocacy for patients seeking to deal with insurance issues or in paying for their products, urging people to go to the organizational websites and to also use their emails: advocate@hemophilia.org and advocacy@hemophiliafed.org.
She also announced that the annual meeting of the HFA was being postponed to Aug. 24-26 at the Hilton Inner Harbor Baltimore, Md.
Dr. Valentino and Ms. Meyers did not provide any disclosure information.
In a webinar conducted on March 20, Leonard Valentino, MD, president and CEO of the National Hemophilia Foundation (NHF), provided
Overall, the risk of comorbidities is no different in the bleeding disorders population than in the general population, and similar precautions should be maintained, Dr. Valentino stated. He listed some of the at-risk populations as designated by the Centers for Disease Control and Prevention.
In particular, he pointed out that, when the CDC referred to a greater risk of COVID-19 to individuals with bleeding disorders, the organization was referring to patients with HIV and sickle cell disease. The CDC was not referring to patients with other forms of bleeding disorders, such as hemophilia, Dr. Valentino stated.
All individuals should be following CDC and state and federal recommendations with regard to social distancing and hygiene. However, with regard to immunocompromised individuals, “the two populations we [in the bleeding disorders community] have to be concerned about are those in gene therapy clinical trials and those with inhibitors,” said Dr. Valentino.
Patients in a gene therapy clinical trial should exercise additional precautions because the use of steroids, common in these trials. “Steroids are an immunosuppressive drug, and this would increase one’s risk of infection, including COVID-19,” according to Dr. Valentino.
In addition, “I will say, if you have hemophilia and an inhibitor [an antibody to clotting factor treatment], that may alter the immune system, and we don’t know what the implication of that is in terms of coronavirus infection and COVID-19 disease. So people with an inhibitor should take special precautions to limit their exposures.”
Patients with a port should not need to have extra concerns regarding COVID-19, but they should continue to exercise the good hygiene that has always been essential, according to Dr. Valentino.
Dr. Valentino asked: Are patients with a bleeding disorder who become infected with COVID-19 more susceptible to a bleed? “You shouldn’t be more susceptible to bleeding except if you have severe cough, and that cough could result in bleeding to the head,” he answered.
If a patient needs to go to the emergency department for a bleed or possible COVID-19 infection, they should wear a face mask if they are sick to prevent spreading of disease. “This is really the only instance where a face mask may be beneficial” in that it limits other people’s exposure to your infection. It is especially important to call ahead before visiting the doctor or going to the emergency department. “Make sure that they’re aware that you’re coming.”
Of particular concern to patients is the amount of factor product they should have on hand. The current CDC recommendation is a 30-day supply of medicines, but that is misleading, because it refers to general medications, such as high-blood pressure medicine, and not factor products. “The current MASAC [NHF’s Medical and Scientific Advisory Council] recommendation is to have a 14-day supply of factor products available to you,” said Dr. Valentino, “and one should reorder when you have a 1-week supply.”
MASAC has issued a letter on the crisis on the NHF website.
These recommendations should not be exceeded in order to ensure that there is enough factor available to all patients, he added. Hoarding is discouraged, and there are no concerns as yet of factor running out. “We have had conversations with manufacturers and … the supply chain is robust.” The greater concern is with regard to ancillary supplies in the hospital that a hemophilia patient may require during treatment.
Patients and practitioners should consult the COVID-19 pages of both the NHF and Hemophilia Federation of America (HFA) websites. This includes a Health and Wellness update by Dr. Valentino.
With regard to financial issues, he and Sharon Meyers, CEO and president of the HFA, spoke, stating that both NHF and HFA have advocacy for patients seeking to deal with insurance issues or in paying for their products, urging people to go to the organizational websites and to also use their emails: advocate@hemophilia.org and advocacy@hemophiliafed.org.
She also announced that the annual meeting of the HFA was being postponed to Aug. 24-26 at the Hilton Inner Harbor Baltimore, Md.
Dr. Valentino and Ms. Meyers did not provide any disclosure information.
Low fitness level linked to higher risk of heart failure in diabetes
PHOENIX – Lower baseline fitness and greater decline in fitness over time are independently associated with a higher risk of heart failure in patients with diabetes, results from a large analysis showed.
“Diabetes is an important risk factor for the development of heart failure, and the diagnosis of diabetes in newly diagnosed cases of heart failure has been increasing,” Ambarish Pandey, MD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Type 2 diabetes is associated with increased burden of traditional risk factors such as hypertension, kidney dysfunction, and dyslipidemia – each of which in turn increase the risk of both atherothrombotic disease as well as heart failure.”
Recent data from the Swedish National Diabetes Register have shown that optimal management of these risk factors in patients with type 2 diabetes can actually mitigate the risk of atherosclerotic events such as acute MI, but the risk of heart failure does not significantly lower with optimal management of these traditional cardiovascular risk factors (N Engl J Med. 2018;379:633-44). “These findings highlight that novel approaches that go beyond just managing traditional cardiovascular risk factors are needed for prevention of heart failure in patients with type 2 diabetes,” said Dr. Pandey, of the division of cardiology at the University of Texas Southwestern Medical Center, Dallas. “Our group has demonstrated that physical inactivity and low levels of fitness are associated with a higher risk of heart failure. We have also shown that the protective effect of physical activity against heart failure risk is stronger against heart failure with preserved ejection fraction, which is a subtype of heart failure that is increasing in prevalence and has no effective therapies.”
Dr. Pandey and his colleagues set out to test the research hypothesis that fitness decline and increases in body mass index over time are significantly associated with a higher risk of heart failure. To do this, they drew from the LookAHEAD Trial, a multicenter analysis of 5,145 overweight or obese patients with type 2 diabetes who were randomized to an intensive lifestyle intervention or to usual care. The intervention consisted of a caloric intake goal of 1,200 to 1,800 kcal per day and engaging in at least 175 minutes per week of physical activity. Participants were stratified into one of three fitness group levels: low, moderate, and high, from 5 metabolic equivalents (METs) in the lowest fitness tertile to 9 METs in the highest fitness tertile. The primary outcome of the trial was adverse cardiovascular events. The intervention was implemented for almost 10 years, and patients were followed for up to 12 years from baseline.
The heart failure outcomes were not systematically adjudicated in the primary LookAHEAD trial, so Dr. Pandey and colleagues conducted an ancillary study of all incident hospitalizations in the study and followed them for 2 additional years. Overall, the researchers identified 257 incident heart failure events. The cumulative incidence of heart failure for the usual care versus the intensive lifestyle intervention arm was not statistically different (an event rate of 4.53 vs. 4.32 per 1,000 person-years, respectively; hazard ratio, 0.96). “This demonstrated that the intensive lifestyle intervention in the LookAHEAD trial did not significantly modify the risk of heart failure,” Dr. Pandey said.
However, an adjusted analysis revealed that the risk of heart failure was 39% lower in the moderately fit group and 62% lower in the high fit group, compared with the low-fitness group. Among heart failure subtypes, the risk of heart failure with preserved ejection fraction (HFpEF) was 40% lower in the moderately fit group and 77% lower in the high-fitness group. On the other hand, baseline level of fitness level was not associated with risk of heart failure reduced ejection fraction (HFrEF) after the researchers adjusted for cardiovascular risk factors.
Next, Dr. Pandey and his colleagues used Cox modeling to examine the association of baseline and longitudinal changes in fitness and BMI with risk of heart failure. For change in fitness and BMI analysis, they used the 4-year follow-up data in 3,092 participants who underwent repeat fitness testing and had available data on BMI. They excluded patients who developed heart failure within the first 4 years of the study.
The mean age of the ancillary study population was about 60 years, and there was a lower proportion of women in the high fitness tertile (41%). The researchers observed a graded, inverse association between higher fitness levels and lower risk of heart failure such that increasing fitness from baseline was associated with a substantial decrease in the risk of heart failure. Specifically, a 10% decline in fitness over the 4 years of follow-up was associated with a 11% increase in the overall risk of heart failure (HR, 1.11). “This was largely consistent with the two heart failure subtypes,” he said. Similarly, a 10% increase in BMI over the 4 years of follow-up was associated with a 25% increase in the overall risk of heart failure (HR 1.25). On the other hand, a 10% decrease BMI was associated with a 20% decrease in the risk of heart failure (HR .80). This was also largely consistent for both heart failure subtypes. According to co-lead investigator Kershaw Patel, MD, “these findings suggest that therapies targeting large and sustained improvements in fitness and weight loss may modify the risk of heart failure among patients with diabetes.”
“Lower fitness at baseline was more strongly associated with the risk of HFpEF vs. HFrEF, and greater weight loss over follow-up is associated with a lower risk of heart failure independent of changes in other risk factors,” Dr. Pandey concluded at the meeting, which was sponsored by the American Heart Association.
In an interview, session moderator Joshua J. Joseph, MD, said that it remains unclear what type of setting is ideal for carrying out cardiorespiratory fitness in this patient population. “What is the supervision needed for that to occur?” asked Dr. Joseph, of The Ohio State University, Columbus. “Can patients do this on their own, or do they need guidance? What is the best approach? That’s the question we all have to answer individually in our own communities.”
Dr. Pandey reported having no disclosures.
SOURCE: Pandey A. Epi/Lifestyle 2020, Abstract 16.
PHOENIX – Lower baseline fitness and greater decline in fitness over time are independently associated with a higher risk of heart failure in patients with diabetes, results from a large analysis showed.
“Diabetes is an important risk factor for the development of heart failure, and the diagnosis of diabetes in newly diagnosed cases of heart failure has been increasing,” Ambarish Pandey, MD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Type 2 diabetes is associated with increased burden of traditional risk factors such as hypertension, kidney dysfunction, and dyslipidemia – each of which in turn increase the risk of both atherothrombotic disease as well as heart failure.”
Recent data from the Swedish National Diabetes Register have shown that optimal management of these risk factors in patients with type 2 diabetes can actually mitigate the risk of atherosclerotic events such as acute MI, but the risk of heart failure does not significantly lower with optimal management of these traditional cardiovascular risk factors (N Engl J Med. 2018;379:633-44). “These findings highlight that novel approaches that go beyond just managing traditional cardiovascular risk factors are needed for prevention of heart failure in patients with type 2 diabetes,” said Dr. Pandey, of the division of cardiology at the University of Texas Southwestern Medical Center, Dallas. “Our group has demonstrated that physical inactivity and low levels of fitness are associated with a higher risk of heart failure. We have also shown that the protective effect of physical activity against heart failure risk is stronger against heart failure with preserved ejection fraction, which is a subtype of heart failure that is increasing in prevalence and has no effective therapies.”
Dr. Pandey and his colleagues set out to test the research hypothesis that fitness decline and increases in body mass index over time are significantly associated with a higher risk of heart failure. To do this, they drew from the LookAHEAD Trial, a multicenter analysis of 5,145 overweight or obese patients with type 2 diabetes who were randomized to an intensive lifestyle intervention or to usual care. The intervention consisted of a caloric intake goal of 1,200 to 1,800 kcal per day and engaging in at least 175 minutes per week of physical activity. Participants were stratified into one of three fitness group levels: low, moderate, and high, from 5 metabolic equivalents (METs) in the lowest fitness tertile to 9 METs in the highest fitness tertile. The primary outcome of the trial was adverse cardiovascular events. The intervention was implemented for almost 10 years, and patients were followed for up to 12 years from baseline.
The heart failure outcomes were not systematically adjudicated in the primary LookAHEAD trial, so Dr. Pandey and colleagues conducted an ancillary study of all incident hospitalizations in the study and followed them for 2 additional years. Overall, the researchers identified 257 incident heart failure events. The cumulative incidence of heart failure for the usual care versus the intensive lifestyle intervention arm was not statistically different (an event rate of 4.53 vs. 4.32 per 1,000 person-years, respectively; hazard ratio, 0.96). “This demonstrated that the intensive lifestyle intervention in the LookAHEAD trial did not significantly modify the risk of heart failure,” Dr. Pandey said.
However, an adjusted analysis revealed that the risk of heart failure was 39% lower in the moderately fit group and 62% lower in the high fit group, compared with the low-fitness group. Among heart failure subtypes, the risk of heart failure with preserved ejection fraction (HFpEF) was 40% lower in the moderately fit group and 77% lower in the high-fitness group. On the other hand, baseline level of fitness level was not associated with risk of heart failure reduced ejection fraction (HFrEF) after the researchers adjusted for cardiovascular risk factors.
Next, Dr. Pandey and his colleagues used Cox modeling to examine the association of baseline and longitudinal changes in fitness and BMI with risk of heart failure. For change in fitness and BMI analysis, they used the 4-year follow-up data in 3,092 participants who underwent repeat fitness testing and had available data on BMI. They excluded patients who developed heart failure within the first 4 years of the study.
The mean age of the ancillary study population was about 60 years, and there was a lower proportion of women in the high fitness tertile (41%). The researchers observed a graded, inverse association between higher fitness levels and lower risk of heart failure such that increasing fitness from baseline was associated with a substantial decrease in the risk of heart failure. Specifically, a 10% decline in fitness over the 4 years of follow-up was associated with a 11% increase in the overall risk of heart failure (HR, 1.11). “This was largely consistent with the two heart failure subtypes,” he said. Similarly, a 10% increase in BMI over the 4 years of follow-up was associated with a 25% increase in the overall risk of heart failure (HR 1.25). On the other hand, a 10% decrease BMI was associated with a 20% decrease in the risk of heart failure (HR .80). This was also largely consistent for both heart failure subtypes. According to co-lead investigator Kershaw Patel, MD, “these findings suggest that therapies targeting large and sustained improvements in fitness and weight loss may modify the risk of heart failure among patients with diabetes.”
“Lower fitness at baseline was more strongly associated with the risk of HFpEF vs. HFrEF, and greater weight loss over follow-up is associated with a lower risk of heart failure independent of changes in other risk factors,” Dr. Pandey concluded at the meeting, which was sponsored by the American Heart Association.
In an interview, session moderator Joshua J. Joseph, MD, said that it remains unclear what type of setting is ideal for carrying out cardiorespiratory fitness in this patient population. “What is the supervision needed for that to occur?” asked Dr. Joseph, of The Ohio State University, Columbus. “Can patients do this on their own, or do they need guidance? What is the best approach? That’s the question we all have to answer individually in our own communities.”
Dr. Pandey reported having no disclosures.
SOURCE: Pandey A. Epi/Lifestyle 2020, Abstract 16.
PHOENIX – Lower baseline fitness and greater decline in fitness over time are independently associated with a higher risk of heart failure in patients with diabetes, results from a large analysis showed.
“Diabetes is an important risk factor for the development of heart failure, and the diagnosis of diabetes in newly diagnosed cases of heart failure has been increasing,” Ambarish Pandey, MD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “Type 2 diabetes is associated with increased burden of traditional risk factors such as hypertension, kidney dysfunction, and dyslipidemia – each of which in turn increase the risk of both atherothrombotic disease as well as heart failure.”
Recent data from the Swedish National Diabetes Register have shown that optimal management of these risk factors in patients with type 2 diabetes can actually mitigate the risk of atherosclerotic events such as acute MI, but the risk of heart failure does not significantly lower with optimal management of these traditional cardiovascular risk factors (N Engl J Med. 2018;379:633-44). “These findings highlight that novel approaches that go beyond just managing traditional cardiovascular risk factors are needed for prevention of heart failure in patients with type 2 diabetes,” said Dr. Pandey, of the division of cardiology at the University of Texas Southwestern Medical Center, Dallas. “Our group has demonstrated that physical inactivity and low levels of fitness are associated with a higher risk of heart failure. We have also shown that the protective effect of physical activity against heart failure risk is stronger against heart failure with preserved ejection fraction, which is a subtype of heart failure that is increasing in prevalence and has no effective therapies.”
Dr. Pandey and his colleagues set out to test the research hypothesis that fitness decline and increases in body mass index over time are significantly associated with a higher risk of heart failure. To do this, they drew from the LookAHEAD Trial, a multicenter analysis of 5,145 overweight or obese patients with type 2 diabetes who were randomized to an intensive lifestyle intervention or to usual care. The intervention consisted of a caloric intake goal of 1,200 to 1,800 kcal per day and engaging in at least 175 minutes per week of physical activity. Participants were stratified into one of three fitness group levels: low, moderate, and high, from 5 metabolic equivalents (METs) in the lowest fitness tertile to 9 METs in the highest fitness tertile. The primary outcome of the trial was adverse cardiovascular events. The intervention was implemented for almost 10 years, and patients were followed for up to 12 years from baseline.
The heart failure outcomes were not systematically adjudicated in the primary LookAHEAD trial, so Dr. Pandey and colleagues conducted an ancillary study of all incident hospitalizations in the study and followed them for 2 additional years. Overall, the researchers identified 257 incident heart failure events. The cumulative incidence of heart failure for the usual care versus the intensive lifestyle intervention arm was not statistically different (an event rate of 4.53 vs. 4.32 per 1,000 person-years, respectively; hazard ratio, 0.96). “This demonstrated that the intensive lifestyle intervention in the LookAHEAD trial did not significantly modify the risk of heart failure,” Dr. Pandey said.
However, an adjusted analysis revealed that the risk of heart failure was 39% lower in the moderately fit group and 62% lower in the high fit group, compared with the low-fitness group. Among heart failure subtypes, the risk of heart failure with preserved ejection fraction (HFpEF) was 40% lower in the moderately fit group and 77% lower in the high-fitness group. On the other hand, baseline level of fitness level was not associated with risk of heart failure reduced ejection fraction (HFrEF) after the researchers adjusted for cardiovascular risk factors.
Next, Dr. Pandey and his colleagues used Cox modeling to examine the association of baseline and longitudinal changes in fitness and BMI with risk of heart failure. For change in fitness and BMI analysis, they used the 4-year follow-up data in 3,092 participants who underwent repeat fitness testing and had available data on BMI. They excluded patients who developed heart failure within the first 4 years of the study.
The mean age of the ancillary study population was about 60 years, and there was a lower proportion of women in the high fitness tertile (41%). The researchers observed a graded, inverse association between higher fitness levels and lower risk of heart failure such that increasing fitness from baseline was associated with a substantial decrease in the risk of heart failure. Specifically, a 10% decline in fitness over the 4 years of follow-up was associated with a 11% increase in the overall risk of heart failure (HR, 1.11). “This was largely consistent with the two heart failure subtypes,” he said. Similarly, a 10% increase in BMI over the 4 years of follow-up was associated with a 25% increase in the overall risk of heart failure (HR 1.25). On the other hand, a 10% decrease BMI was associated with a 20% decrease in the risk of heart failure (HR .80). This was also largely consistent for both heart failure subtypes. According to co-lead investigator Kershaw Patel, MD, “these findings suggest that therapies targeting large and sustained improvements in fitness and weight loss may modify the risk of heart failure among patients with diabetes.”
“Lower fitness at baseline was more strongly associated with the risk of HFpEF vs. HFrEF, and greater weight loss over follow-up is associated with a lower risk of heart failure independent of changes in other risk factors,” Dr. Pandey concluded at the meeting, which was sponsored by the American Heart Association.
In an interview, session moderator Joshua J. Joseph, MD, said that it remains unclear what type of setting is ideal for carrying out cardiorespiratory fitness in this patient population. “What is the supervision needed for that to occur?” asked Dr. Joseph, of The Ohio State University, Columbus. “Can patients do this on their own, or do they need guidance? What is the best approach? That’s the question we all have to answer individually in our own communities.”
Dr. Pandey reported having no disclosures.
SOURCE: Pandey A. Epi/Lifestyle 2020, Abstract 16.
REPORTING FROM EPI/LIFESTYLE 2020
Are CRMO and SAPHO syndrome one and the same?
MAUI, HAWAII – Chronic recurrent multifocal osteomyelitis (CRMO) in children and SAPHO syndrome in adults may well be a single clinical syndrome.
That contention, recently put forth by Austrian investigators, resonates with Anne M. Stevens, MD, PhD, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
“Is CRMO just for kids? No,” she asserted at the 2020 Rheumatology Winter Clinical Symposium.
First off, she noted that the nomenclature is shifting: The more familiar acronym CRMO is giving way to CNO (chronic nonbacterial osteomyelitis) in light of evidence that roughly 30% of patients with CRMO start out with a single characteristic bone lesion, with the disease turning multifocal in the subsequent 4 years in the great majority of cases.
SAPHO syndrome – an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis – a formerly obscure disease entity first described in 1987 in France, has suddenly become a trendy research topic, with three small studies presented at the 2019 annual meeting of the American College of Rheumatology.
CNO is a pediatric autoinflammatory bone disease characterized by sterile bone lesions, most often on the clavicle, spine, mandible, and lower extremities. It is marked by prominent focal bone and/or joint pain, worse at night, with or without swelling. With no agreed-upon diagnostic criteria or biomarkers, CNO is a diagnosis of exclusion. Two-thirds of the time the condition is initially misdiagnosed as bacterial osteomyelitis or a malignant tumor.
Austrian investigators at the University of Graz recently conducted a retrospective comparison of 24 pediatric patients diagnosed with CNO and 10 adults with SAPHO syndrome. The median age at diagnosis of CNO was 12.3 years versus 32.5 years for SAPHO syndrome. The two groups shared compelling similarities in mean number of bone lesions, prevalence of skin involvement, and other aspects of initial clinical presentation, as well as laboratory and histopathologic findings on bone biopsy.
There were, however, several notable clinical differences in this small dataset: CNO bone lesions affected mainly the lower extremities, clavicle, spine, and mandible, while SAPHO syndrome more commonly involved the sternum (50% vs. 8%) and vertebrae (50% vs. 21%). Also, the most frequent cutaneous manifestation was palmoplantar pustulosis in adults with SAPHO syndrome, while severe acne predominated in children with CNO. In both children and adults, the skin lesions most often arose after the bone symptoms, making early diagnosis a challenge.
Another similarity: Although there have been no randomized treatment trials in either CNO or SAPHO syndrome, case series suggest the same treatments are effective for both, with NSAIDs as first line, followed by nonbiologic disease-modifying antirheumatic drugs, tumor necrosis factor (TNF) inhibitors, or bisphosphonates.
CNO diagnosis, treatment, and follow-up
Various investigators have pegged the sensitivity of physical examination for diagnosis of CNO at 31%, radiographs at a lowly 13%, and bone scintigraphy at 74%, all in comparison with MRI.
“Our go-to now is MRI with STIR [short tau inversion recovery],” according to Dr. Stevens. “There’s no contrast – so no IV – no radiation, and it’s fast, 20 minutes for a whole body MRI in a little kid, 45 minutes in a big one.”
Insurers are reluctant to pay for serial whole-body MRIs for patient follow-up, so it’s often necessary to order a series of images covering different body parts.
Her University of Washington colleague Dan Zhao, MD, PhD, is developing infrared thermal imaging as an inexpensive, convenient alternative to MRI which could theoretically be done at home. In a pilot study in 30 children with CNO and 31 controls, inflamed leg segments showed significantly higher temperatures. Larger studies are planned.
Dr. Stevens advised leaning towards a diagnosis of CNO with avoidance of bone biopsy in a patient with multifocal osteomyelitis at the typical sites, a normal CBC, the typical extraosseous manifestations, and normal or only mildly elevated erythrocyte sedimentation rate and C-reactive protein in an otherwise well-appearing child. In contrast, strongly consider a bone biopsy to rule out malignancy or infection if the child has unexplained highly elevated C-reactive protein and erythrocyte sedimentation rate, cytopenia, high fever, excessive pain, lymphadenopathy, hepatosplenomegaly, or suspicious imaging findings.
German rheumatologists have developed a clinical score for diagnosis of CNO. A normal blood cell count gets 13 points; symmetric bone lesions 10; lesions with marginal sclerosis 10; a normal body temperature 9; two or more radiologically proven lesions 7; a C-reactive protein of 1 mg/dL or greater 6; and vertebral, clavicular, or sternal lesions 8. A score of 39 points or more out of a possible 63 had a 97% positive predictive value for CNO in a retrospective study of 224 children with CNO, proven bacterial osteomyelitis, or malignant bone tumors. A score of 28 points or less had a 97% negative predictive value for CNO. An indeterminate score of 29-38 warrants close monitoring.
The scoring system hasn’t been validated, but most pediatric rheumatologists agree that it’s useful, according to Dr. Stevens.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) is in the process of developing standardized diagnostic and classification criteria and treatment plans for CNO. Dr. Zhao was first author of a CARRA consensus treatment plan for CNO refractory to NSAID monotherapy. The plan for the first 12 months includes three options: methotrexate or sulfasalazine, TNF inhibitors with or without methotrexate, and bisphosphonates.
“The main point of this is you try a medicine and then wait 3 months. If they’re not responding then, switch medicines or add another drug. Monitor every 3 months based upon pain,” she said.
Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.
MAUI, HAWAII – Chronic recurrent multifocal osteomyelitis (CRMO) in children and SAPHO syndrome in adults may well be a single clinical syndrome.
That contention, recently put forth by Austrian investigators, resonates with Anne M. Stevens, MD, PhD, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
“Is CRMO just for kids? No,” she asserted at the 2020 Rheumatology Winter Clinical Symposium.
First off, she noted that the nomenclature is shifting: The more familiar acronym CRMO is giving way to CNO (chronic nonbacterial osteomyelitis) in light of evidence that roughly 30% of patients with CRMO start out with a single characteristic bone lesion, with the disease turning multifocal in the subsequent 4 years in the great majority of cases.
SAPHO syndrome – an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis – a formerly obscure disease entity first described in 1987 in France, has suddenly become a trendy research topic, with three small studies presented at the 2019 annual meeting of the American College of Rheumatology.
CNO is a pediatric autoinflammatory bone disease characterized by sterile bone lesions, most often on the clavicle, spine, mandible, and lower extremities. It is marked by prominent focal bone and/or joint pain, worse at night, with or without swelling. With no agreed-upon diagnostic criteria or biomarkers, CNO is a diagnosis of exclusion. Two-thirds of the time the condition is initially misdiagnosed as bacterial osteomyelitis or a malignant tumor.
Austrian investigators at the University of Graz recently conducted a retrospective comparison of 24 pediatric patients diagnosed with CNO and 10 adults with SAPHO syndrome. The median age at diagnosis of CNO was 12.3 years versus 32.5 years for SAPHO syndrome. The two groups shared compelling similarities in mean number of bone lesions, prevalence of skin involvement, and other aspects of initial clinical presentation, as well as laboratory and histopathologic findings on bone biopsy.
There were, however, several notable clinical differences in this small dataset: CNO bone lesions affected mainly the lower extremities, clavicle, spine, and mandible, while SAPHO syndrome more commonly involved the sternum (50% vs. 8%) and vertebrae (50% vs. 21%). Also, the most frequent cutaneous manifestation was palmoplantar pustulosis in adults with SAPHO syndrome, while severe acne predominated in children with CNO. In both children and adults, the skin lesions most often arose after the bone symptoms, making early diagnosis a challenge.
Another similarity: Although there have been no randomized treatment trials in either CNO or SAPHO syndrome, case series suggest the same treatments are effective for both, with NSAIDs as first line, followed by nonbiologic disease-modifying antirheumatic drugs, tumor necrosis factor (TNF) inhibitors, or bisphosphonates.
CNO diagnosis, treatment, and follow-up
Various investigators have pegged the sensitivity of physical examination for diagnosis of CNO at 31%, radiographs at a lowly 13%, and bone scintigraphy at 74%, all in comparison with MRI.
“Our go-to now is MRI with STIR [short tau inversion recovery],” according to Dr. Stevens. “There’s no contrast – so no IV – no radiation, and it’s fast, 20 minutes for a whole body MRI in a little kid, 45 minutes in a big one.”
Insurers are reluctant to pay for serial whole-body MRIs for patient follow-up, so it’s often necessary to order a series of images covering different body parts.
Her University of Washington colleague Dan Zhao, MD, PhD, is developing infrared thermal imaging as an inexpensive, convenient alternative to MRI which could theoretically be done at home. In a pilot study in 30 children with CNO and 31 controls, inflamed leg segments showed significantly higher temperatures. Larger studies are planned.
Dr. Stevens advised leaning towards a diagnosis of CNO with avoidance of bone biopsy in a patient with multifocal osteomyelitis at the typical sites, a normal CBC, the typical extraosseous manifestations, and normal or only mildly elevated erythrocyte sedimentation rate and C-reactive protein in an otherwise well-appearing child. In contrast, strongly consider a bone biopsy to rule out malignancy or infection if the child has unexplained highly elevated C-reactive protein and erythrocyte sedimentation rate, cytopenia, high fever, excessive pain, lymphadenopathy, hepatosplenomegaly, or suspicious imaging findings.
German rheumatologists have developed a clinical score for diagnosis of CNO. A normal blood cell count gets 13 points; symmetric bone lesions 10; lesions with marginal sclerosis 10; a normal body temperature 9; two or more radiologically proven lesions 7; a C-reactive protein of 1 mg/dL or greater 6; and vertebral, clavicular, or sternal lesions 8. A score of 39 points or more out of a possible 63 had a 97% positive predictive value for CNO in a retrospective study of 224 children with CNO, proven bacterial osteomyelitis, or malignant bone tumors. A score of 28 points or less had a 97% negative predictive value for CNO. An indeterminate score of 29-38 warrants close monitoring.
The scoring system hasn’t been validated, but most pediatric rheumatologists agree that it’s useful, according to Dr. Stevens.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) is in the process of developing standardized diagnostic and classification criteria and treatment plans for CNO. Dr. Zhao was first author of a CARRA consensus treatment plan for CNO refractory to NSAID monotherapy. The plan for the first 12 months includes three options: methotrexate or sulfasalazine, TNF inhibitors with or without methotrexate, and bisphosphonates.
“The main point of this is you try a medicine and then wait 3 months. If they’re not responding then, switch medicines or add another drug. Monitor every 3 months based upon pain,” she said.
Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.
MAUI, HAWAII – Chronic recurrent multifocal osteomyelitis (CRMO) in children and SAPHO syndrome in adults may well be a single clinical syndrome.
That contention, recently put forth by Austrian investigators, resonates with Anne M. Stevens, MD, PhD, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
“Is CRMO just for kids? No,” she asserted at the 2020 Rheumatology Winter Clinical Symposium.
First off, she noted that the nomenclature is shifting: The more familiar acronym CRMO is giving way to CNO (chronic nonbacterial osteomyelitis) in light of evidence that roughly 30% of patients with CRMO start out with a single characteristic bone lesion, with the disease turning multifocal in the subsequent 4 years in the great majority of cases.
SAPHO syndrome – an acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis – a formerly obscure disease entity first described in 1987 in France, has suddenly become a trendy research topic, with three small studies presented at the 2019 annual meeting of the American College of Rheumatology.
CNO is a pediatric autoinflammatory bone disease characterized by sterile bone lesions, most often on the clavicle, spine, mandible, and lower extremities. It is marked by prominent focal bone and/or joint pain, worse at night, with or without swelling. With no agreed-upon diagnostic criteria or biomarkers, CNO is a diagnosis of exclusion. Two-thirds of the time the condition is initially misdiagnosed as bacterial osteomyelitis or a malignant tumor.
Austrian investigators at the University of Graz recently conducted a retrospective comparison of 24 pediatric patients diagnosed with CNO and 10 adults with SAPHO syndrome. The median age at diagnosis of CNO was 12.3 years versus 32.5 years for SAPHO syndrome. The two groups shared compelling similarities in mean number of bone lesions, prevalence of skin involvement, and other aspects of initial clinical presentation, as well as laboratory and histopathologic findings on bone biopsy.
There were, however, several notable clinical differences in this small dataset: CNO bone lesions affected mainly the lower extremities, clavicle, spine, and mandible, while SAPHO syndrome more commonly involved the sternum (50% vs. 8%) and vertebrae (50% vs. 21%). Also, the most frequent cutaneous manifestation was palmoplantar pustulosis in adults with SAPHO syndrome, while severe acne predominated in children with CNO. In both children and adults, the skin lesions most often arose after the bone symptoms, making early diagnosis a challenge.
Another similarity: Although there have been no randomized treatment trials in either CNO or SAPHO syndrome, case series suggest the same treatments are effective for both, with NSAIDs as first line, followed by nonbiologic disease-modifying antirheumatic drugs, tumor necrosis factor (TNF) inhibitors, or bisphosphonates.
CNO diagnosis, treatment, and follow-up
Various investigators have pegged the sensitivity of physical examination for diagnosis of CNO at 31%, radiographs at a lowly 13%, and bone scintigraphy at 74%, all in comparison with MRI.
“Our go-to now is MRI with STIR [short tau inversion recovery],” according to Dr. Stevens. “There’s no contrast – so no IV – no radiation, and it’s fast, 20 minutes for a whole body MRI in a little kid, 45 minutes in a big one.”
Insurers are reluctant to pay for serial whole-body MRIs for patient follow-up, so it’s often necessary to order a series of images covering different body parts.
Her University of Washington colleague Dan Zhao, MD, PhD, is developing infrared thermal imaging as an inexpensive, convenient alternative to MRI which could theoretically be done at home. In a pilot study in 30 children with CNO and 31 controls, inflamed leg segments showed significantly higher temperatures. Larger studies are planned.
Dr. Stevens advised leaning towards a diagnosis of CNO with avoidance of bone biopsy in a patient with multifocal osteomyelitis at the typical sites, a normal CBC, the typical extraosseous manifestations, and normal or only mildly elevated erythrocyte sedimentation rate and C-reactive protein in an otherwise well-appearing child. In contrast, strongly consider a bone biopsy to rule out malignancy or infection if the child has unexplained highly elevated C-reactive protein and erythrocyte sedimentation rate, cytopenia, high fever, excessive pain, lymphadenopathy, hepatosplenomegaly, or suspicious imaging findings.
German rheumatologists have developed a clinical score for diagnosis of CNO. A normal blood cell count gets 13 points; symmetric bone lesions 10; lesions with marginal sclerosis 10; a normal body temperature 9; two or more radiologically proven lesions 7; a C-reactive protein of 1 mg/dL or greater 6; and vertebral, clavicular, or sternal lesions 8. A score of 39 points or more out of a possible 63 had a 97% positive predictive value for CNO in a retrospective study of 224 children with CNO, proven bacterial osteomyelitis, or malignant bone tumors. A score of 28 points or less had a 97% negative predictive value for CNO. An indeterminate score of 29-38 warrants close monitoring.
The scoring system hasn’t been validated, but most pediatric rheumatologists agree that it’s useful, according to Dr. Stevens.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) is in the process of developing standardized diagnostic and classification criteria and treatment plans for CNO. Dr. Zhao was first author of a CARRA consensus treatment plan for CNO refractory to NSAID monotherapy. The plan for the first 12 months includes three options: methotrexate or sulfasalazine, TNF inhibitors with or without methotrexate, and bisphosphonates.
“The main point of this is you try a medicine and then wait 3 months. If they’re not responding then, switch medicines or add another drug. Monitor every 3 months based upon pain,” she said.
Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.
EXPERT ANALYSIS FROM RWCS 2020
Conscious sedation during TAVR best for most patients
From the Society for Thoracic Surgeons (STS)/ACC Transcatheter Valve Therapy (TVT) Registry, the group identified 120,080 patients who had TAVR at 559 US sites, from January 2016 to March 2019.
During this time, the percentage of procedures that were done using conscious sedation almost doubled, plateauing in the final 6 months.
And the proportion of sites using any conscious sedation during TAVR increased from 50% to 76%.
The use of this procedure varied widely among the sites: 26% performed >80% of TAVR with conscious sedation, and 13% did not perform any TAVR cases with conscious sedation.
In hospitals in the lowest and highest quartiles of use of conscious sedation during TAVR, this type of sedation was used in a median of 0% of TAVR cases and 91% of cases, respectively.
The researchers used instrumental variable analysis to compare outcomes in patients whose type of anesthesia would differ if they went to a hospital with high or low use of conscious sedation.
Using this method, the use of conscious sedation was associated with a 0.2% absolute risk difference in in-hospital death, the primary study endpoint (P = .010).
And compared with general anesthesia, conscious sedation during TAVR was also associated with a lower rate of 30-day death (2.0% vs 2.5%, respectively), fewer days in the hospital (3.5 vs 4.3 days), and a higher rate of being discharged to home (88.9% vs 86.1%, all P < .001).
“Our results would not apply to those patients who always receive general anesthesia, even at high conscious sedation use centers (eg, patients with severe lung disease on oxygen or significant right ventricular dysfunction),” the authors caution.
Study limitations, next steps
A study limitation is that the registry data did not specify the type of conscious sedation that was used, Cohen acknowledged.
This could vary. For example, a patient could be given a very powerful sedative such as propofol (Diprivan), and his or her respiration and oxygen saturation would be monitored, and an anesthesiologist would be always present. Or the patient could receive sedation like that for angioplasty — diazepam (Valium) or midazolam (Versed) and a narcotic — without an anesthesiologist.
It would be useful to look at the TAVR volumes and compare outcomes within different TAVR volume quartiles, Tang suggested.
In low-volume centers, the anesthesiologist may be uncomfortable with complex cases, whereas larger academic centers would perform more complex procedures and may paradoxically have a slightly higher rate of complications, he speculated.
Future research should investigate what drives the differences in the use of conscious sedation, the authors suggest.
Cohen reports institutional grant support and consulting fees from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott. Butala is funded by the John S. LaDue Memorial Fellowship at Harvard Medical School and reports consulting fees and ownership interest in HiLabs, outside the submitted work. The disclosures of the other authors are listed with the original article.
This article first appeared on Medscape.com.
From the Society for Thoracic Surgeons (STS)/ACC Transcatheter Valve Therapy (TVT) Registry, the group identified 120,080 patients who had TAVR at 559 US sites, from January 2016 to March 2019.
During this time, the percentage of procedures that were done using conscious sedation almost doubled, plateauing in the final 6 months.
And the proportion of sites using any conscious sedation during TAVR increased from 50% to 76%.
The use of this procedure varied widely among the sites: 26% performed >80% of TAVR with conscious sedation, and 13% did not perform any TAVR cases with conscious sedation.
In hospitals in the lowest and highest quartiles of use of conscious sedation during TAVR, this type of sedation was used in a median of 0% of TAVR cases and 91% of cases, respectively.
The researchers used instrumental variable analysis to compare outcomes in patients whose type of anesthesia would differ if they went to a hospital with high or low use of conscious sedation.
Using this method, the use of conscious sedation was associated with a 0.2% absolute risk difference in in-hospital death, the primary study endpoint (P = .010).
And compared with general anesthesia, conscious sedation during TAVR was also associated with a lower rate of 30-day death (2.0% vs 2.5%, respectively), fewer days in the hospital (3.5 vs 4.3 days), and a higher rate of being discharged to home (88.9% vs 86.1%, all P < .001).
“Our results would not apply to those patients who always receive general anesthesia, even at high conscious sedation use centers (eg, patients with severe lung disease on oxygen or significant right ventricular dysfunction),” the authors caution.
Study limitations, next steps
A study limitation is that the registry data did not specify the type of conscious sedation that was used, Cohen acknowledged.
This could vary. For example, a patient could be given a very powerful sedative such as propofol (Diprivan), and his or her respiration and oxygen saturation would be monitored, and an anesthesiologist would be always present. Or the patient could receive sedation like that for angioplasty — diazepam (Valium) or midazolam (Versed) and a narcotic — without an anesthesiologist.
It would be useful to look at the TAVR volumes and compare outcomes within different TAVR volume quartiles, Tang suggested.
In low-volume centers, the anesthesiologist may be uncomfortable with complex cases, whereas larger academic centers would perform more complex procedures and may paradoxically have a slightly higher rate of complications, he speculated.
Future research should investigate what drives the differences in the use of conscious sedation, the authors suggest.
Cohen reports institutional grant support and consulting fees from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott. Butala is funded by the John S. LaDue Memorial Fellowship at Harvard Medical School and reports consulting fees and ownership interest in HiLabs, outside the submitted work. The disclosures of the other authors are listed with the original article.
This article first appeared on Medscape.com.
From the Society for Thoracic Surgeons (STS)/ACC Transcatheter Valve Therapy (TVT) Registry, the group identified 120,080 patients who had TAVR at 559 US sites, from January 2016 to March 2019.
During this time, the percentage of procedures that were done using conscious sedation almost doubled, plateauing in the final 6 months.
And the proportion of sites using any conscious sedation during TAVR increased from 50% to 76%.
The use of this procedure varied widely among the sites: 26% performed >80% of TAVR with conscious sedation, and 13% did not perform any TAVR cases with conscious sedation.
In hospitals in the lowest and highest quartiles of use of conscious sedation during TAVR, this type of sedation was used in a median of 0% of TAVR cases and 91% of cases, respectively.
The researchers used instrumental variable analysis to compare outcomes in patients whose type of anesthesia would differ if they went to a hospital with high or low use of conscious sedation.
Using this method, the use of conscious sedation was associated with a 0.2% absolute risk difference in in-hospital death, the primary study endpoint (P = .010).
And compared with general anesthesia, conscious sedation during TAVR was also associated with a lower rate of 30-day death (2.0% vs 2.5%, respectively), fewer days in the hospital (3.5 vs 4.3 days), and a higher rate of being discharged to home (88.9% vs 86.1%, all P < .001).
“Our results would not apply to those patients who always receive general anesthesia, even at high conscious sedation use centers (eg, patients with severe lung disease on oxygen or significant right ventricular dysfunction),” the authors caution.
Study limitations, next steps
A study limitation is that the registry data did not specify the type of conscious sedation that was used, Cohen acknowledged.
This could vary. For example, a patient could be given a very powerful sedative such as propofol (Diprivan), and his or her respiration and oxygen saturation would be monitored, and an anesthesiologist would be always present. Or the patient could receive sedation like that for angioplasty — diazepam (Valium) or midazolam (Versed) and a narcotic — without an anesthesiologist.
It would be useful to look at the TAVR volumes and compare outcomes within different TAVR volume quartiles, Tang suggested.
In low-volume centers, the anesthesiologist may be uncomfortable with complex cases, whereas larger academic centers would perform more complex procedures and may paradoxically have a slightly higher rate of complications, he speculated.
Future research should investigate what drives the differences in the use of conscious sedation, the authors suggest.
Cohen reports institutional grant support and consulting fees from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott. Butala is funded by the John S. LaDue Memorial Fellowship at Harvard Medical School and reports consulting fees and ownership interest in HiLabs, outside the submitted work. The disclosures of the other authors are listed with the original article.
This article first appeared on Medscape.com.