Pediatrics

Assessing appendicitis in children with initial ultrasound followed by computed tomography in the absence of appendix visualization and presence of secondary signs was the most cost-effective approach, according to data from a modeling study of 10 strategies.

Ultrasound is safer and less expensive than computed tomography and avoids radiation exposure; however, cost-effectiveness models of various approaches to imaging have not been well studied, wrote Rebecca Jennings, MD, of Seattle Children’s Hospital, Washington, and colleagues.

In a study published in Pediatrics, the researchers simulated a hypothetical patient population using a Markov cohort model and compared 10 different strategies including CT only, MRI only, and ultrasound followed by CT or MRI after ultrasounds that are negative or fail to visualize the appendix.

Overall, the most cost-effective strategy for moderate-risk patients was the use of ultrasound followed by CT or MRI if the ultrasound failed to visualize the appendix and secondary signs of inflammation were present in the right lower quadrant. The cost of this strategy was $4,815, with effectiveness of 0.99694 quality-adjusted life-years. “The most cost-effective strategy is highly dependent on a patient’s risk stratification,” the researchers noted. Based on their model, imaging was not cost effective for patients with a prevalence less than 16% or greater than 95%. However, those with appendicitis risk between 16% and 95% and no secondary signs of inflammation can forgo further imaging, even without visualization of the appendix for maximum cost-effectiveness, the researchers said.

The study was limited by several factors, including the inability to account for all potential costs related to imaging and outcomes, lack of accounting for the use of sedation when assessing costs, and inability to separate imaging costs from total hospital costs, the researchers noted. However, the results suggest that tailored imaging approaches based on patient risk are the most cost-effective strategies to assess appendicitis, they said.

“The diagnosis and exclusion of appendicitis continues to be one of the primary concerns of providers who care for children with abdominal pain,” wrote Rebecca M. Rentea, MD, and Charles L. Snyder, MD, of Children’s Mercy Hospital Kansas City, Mo., in an accompanying editorial (Pediatrics. 2020 Feb;145:e20193349).

“The best diagnostic and imaging approach to appendicitis has been a topic of interest for some time, and improvements such as appendicitis scoring systems, decreased use of ionized radiation, and adoption of clinical algorithms have been incremental but steady,” they said. Despite the potential of missed appendicitis, the use of an algorithm based on an initial ultrasound and previous possibility of appendicitis described in the study was the most cost effective, they said. In addition, “the ability to visualize the appendix did not alter the most cost-effective approach in those with a moderate risk of appendicitis (most patients),” they concluded.

The study was supported by the University of Washington and Seattle Children’s Hospital Quality Improvement Scholars Program. The researchers had no financial conflicts to disclose.

Dr. Rentea and Dr. Snyder had no financial conflicts to disclose.

SOURCE: Jennings R et al. Pediatrics. 2020. doi: 10.1542/peds.2019-1352.

Assessing appendicitis in children with initial ultrasound followed by computed tomography in the absence of appendix visualization and presence of secondary signs was the most cost-effective approach, according to data from a modeling study of 10 strategies.

Ultrasound is safer and less expensive than computed tomography and avoids radiation exposure; however, cost-effectiveness models of various approaches to imaging have not been well studied, wrote Rebecca Jennings, MD, of Seattle Children’s Hospital, Washington, and colleagues.

In a study published in Pediatrics, the researchers simulated a hypothetical patient population using a Markov cohort model and compared 10 different strategies including CT only, MRI only, and ultrasound followed by CT or MRI after ultrasounds that are negative or fail to visualize the appendix.

Overall, the most cost-effective strategy for moderate-risk patients was the use of ultrasound followed by CT or MRI if the ultrasound failed to visualize the appendix and secondary signs of inflammation were present in the right lower quadrant. The cost of this strategy was $4,815, with effectiveness of 0.99694 quality-adjusted life-years. “The most cost-effective strategy is highly dependent on a patient’s risk stratification,” the researchers noted. Based on their model, imaging was not cost effective for patients with a prevalence less than 16% or greater than 95%. However, those with appendicitis risk between 16% and 95% and no secondary signs of inflammation can forgo further imaging, even without visualization of the appendix for maximum cost-effectiveness, the researchers said.

The study was limited by several factors, including the inability to account for all potential costs related to imaging and outcomes, lack of accounting for the use of sedation when assessing costs, and inability to separate imaging costs from total hospital costs, the researchers noted. However, the results suggest that tailored imaging approaches based on patient risk are the most cost-effective strategies to assess appendicitis, they said.

“The diagnosis and exclusion of appendicitis continues to be one of the primary concerns of providers who care for children with abdominal pain,” wrote Rebecca M. Rentea, MD, and Charles L. Snyder, MD, of Children’s Mercy Hospital Kansas City, Mo., in an accompanying editorial (Pediatrics. 2020 Feb;145:e20193349).

“The best diagnostic and imaging approach to appendicitis has been a topic of interest for some time, and improvements such as appendicitis scoring systems, decreased use of ionized radiation, and adoption of clinical algorithms have been incremental but steady,” they said. Despite the potential of missed appendicitis, the use of an algorithm based on an initial ultrasound and previous possibility of appendicitis described in the study was the most cost effective, they said. In addition, “the ability to visualize the appendix did not alter the most cost-effective approach in those with a moderate risk of appendicitis (most patients),” they concluded.

The study was supported by the University of Washington and Seattle Children’s Hospital Quality Improvement Scholars Program. The researchers had no financial conflicts to disclose.

Dr. Rentea and Dr. Snyder had no financial conflicts to disclose.

SOURCE: Jennings R et al. Pediatrics. 2020. doi: 10.1542/peds.2019-1352.

Assessing appendicitis in children with initial ultrasound followed by computed tomography in the absence of appendix visualization and presence of secondary signs was the most cost-effective approach, according to data from a modeling study of 10 strategies.

Ultrasound is safer and less expensive than computed tomography and avoids radiation exposure; however, cost-effectiveness models of various approaches to imaging have not been well studied, wrote Rebecca Jennings, MD, of Seattle Children’s Hospital, Washington, and colleagues.

In a study published in Pediatrics, the researchers simulated a hypothetical patient population using a Markov cohort model and compared 10 different strategies including CT only, MRI only, and ultrasound followed by CT or MRI after ultrasounds that are negative or fail to visualize the appendix.

Overall, the most cost-effective strategy for moderate-risk patients was the use of ultrasound followed by CT or MRI if the ultrasound failed to visualize the appendix and secondary signs of inflammation were present in the right lower quadrant. The cost of this strategy was $4,815, with effectiveness of 0.99694 quality-adjusted life-years. “The most cost-effective strategy is highly dependent on a patient’s risk stratification,” the researchers noted. Based on their model, imaging was not cost effective for patients with a prevalence less than 16% or greater than 95%. However, those with appendicitis risk between 16% and 95% and no secondary signs of inflammation can forgo further imaging, even without visualization of the appendix for maximum cost-effectiveness, the researchers said.

The study was limited by several factors, including the inability to account for all potential costs related to imaging and outcomes, lack of accounting for the use of sedation when assessing costs, and inability to separate imaging costs from total hospital costs, the researchers noted. However, the results suggest that tailored imaging approaches based on patient risk are the most cost-effective strategies to assess appendicitis, they said.

“The diagnosis and exclusion of appendicitis continues to be one of the primary concerns of providers who care for children with abdominal pain,” wrote Rebecca M. Rentea, MD, and Charles L. Snyder, MD, of Children’s Mercy Hospital Kansas City, Mo., in an accompanying editorial (Pediatrics. 2020 Feb;145:e20193349).

“The best diagnostic and imaging approach to appendicitis has been a topic of interest for some time, and improvements such as appendicitis scoring systems, decreased use of ionized radiation, and adoption of clinical algorithms have been incremental but steady,” they said. Despite the potential of missed appendicitis, the use of an algorithm based on an initial ultrasound and previous possibility of appendicitis described in the study was the most cost effective, they said. In addition, “the ability to visualize the appendix did not alter the most cost-effective approach in those with a moderate risk of appendicitis (most patients),” they concluded.

The study was supported by the University of Washington and Seattle Children’s Hospital Quality Improvement Scholars Program. The researchers had no financial conflicts to disclose.

Dr. Rentea and Dr. Snyder had no financial conflicts to disclose.

SOURCE: Jennings R et al. Pediatrics. 2020. doi: 10.1542/peds.2019-1352.

Most patients with epidermolysis bullosa who use topical products choose antimicrobials, according to data from a survey of 202 children and adults.

Management of epidermolysis bullosa (EB) involves a combination of skin protection and infection management, but patient home care practices have not been well studied, wrote Leila Shayegan of Columbia University, New York, and colleagues.

In a study published in Pediatric Dermatology, the researchers surveyed 202 patients who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database during 2017. The patients ranged in age from 1 month to 62 years with an average age of 11 years; 52% were female. The patients represented a range of EB subtypes, including 130 patients with dystrophic EB, 51 patients with EB simplex, 21 with junctional EB, and 3 patients each with Kindler syndrome and unspecified subtypes.

Overall, most of the patients reported cleaning their skin either every day (37%) or every other day (32%). Of the 188 patients who reported using topical products on their wounds, 131 (70%) said they used at least one antimicrobial product, while 125 patients (66%) reported using at least one emollient; 32 (17%) used emollients only, and 21(11%) reported no use of topical products.

The most popular topical antibiotics were mupirocin (31%) and bacitracin (31%). In addition, 14% of respondents used silver-containing products, and 16% used medical-grade honey. Roughly half (51%) of patients who reported use of at least one antimicrobial product used two or more different antimicrobial products.

A total of 38% of patients used only water for cleansing. Of the 131 patients who reported using additives in their cleansing water, 57% added salt, 54% added bleach, 27% added vinegar, and 26% reported “other” additive use, which could include Epsom salt, baking soda, oatmeal, or essential oils, the researchers said. The concentrations of these additives ranged from barely effective 0.002% sodium hypochlorite and 0.002% acetic acid solutions to potentially cytotoxic solutions of 0.09% sodium hypochlorite and 0.156% acetic acid.

“Although the survey was not designed to correlate skin care practices with wound culture results and resistance patterns, widespread use of topical antimicrobials described among EB patients highlights the need for increased emphasis on antibiotic stewardship,” the researchers noted. They added that health care providers should educate patients and families not only about mindful use of antibiotics, but also appropriate concentrations of cleansing additives.

“Optimizing EB patient home skin care routines, along with future longitudinal studies on the impact of EB skin care interventions on microbial resistance patterns, wound healing and [squamous cell carcinoma] risk are necessary to improve outcomes for patients with EB,” they emphasized.

The Epidermolysis Bullosa Clinical Characterization and Outcomes Database used in the study is funded by the Epidermolysis Bullosa Research Partnership and the Epidermolysis Bullosa Medical Research Foundation. Ms. Shayegan had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies including Abeona Therapeutics, Castle Creek Pharmaceuticals, Fibrocell Science, ProQR, and Scioderm.

SOURCE: Shayegan L et al. Pediatr Dermatol. 2020. doi: 10.1111/pde.14102.

Most patients with epidermolysis bullosa who use topical products choose antimicrobials, according to data from a survey of 202 children and adults.

Management of epidermolysis bullosa (EB) involves a combination of skin protection and infection management, but patient home care practices have not been well studied, wrote Leila Shayegan of Columbia University, New York, and colleagues.

In a study published in Pediatric Dermatology, the researchers surveyed 202 patients who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database during 2017. The patients ranged in age from 1 month to 62 years with an average age of 11 years; 52% were female. The patients represented a range of EB subtypes, including 130 patients with dystrophic EB, 51 patients with EB simplex, 21 with junctional EB, and 3 patients each with Kindler syndrome and unspecified subtypes.

Overall, most of the patients reported cleaning their skin either every day (37%) or every other day (32%). Of the 188 patients who reported using topical products on their wounds, 131 (70%) said they used at least one antimicrobial product, while 125 patients (66%) reported using at least one emollient; 32 (17%) used emollients only, and 21(11%) reported no use of topical products.

The most popular topical antibiotics were mupirocin (31%) and bacitracin (31%). In addition, 14% of respondents used silver-containing products, and 16% used medical-grade honey. Roughly half (51%) of patients who reported use of at least one antimicrobial product used two or more different antimicrobial products.

A total of 38% of patients used only water for cleansing. Of the 131 patients who reported using additives in their cleansing water, 57% added salt, 54% added bleach, 27% added vinegar, and 26% reported “other” additive use, which could include Epsom salt, baking soda, oatmeal, or essential oils, the researchers said. The concentrations of these additives ranged from barely effective 0.002% sodium hypochlorite and 0.002% acetic acid solutions to potentially cytotoxic solutions of 0.09% sodium hypochlorite and 0.156% acetic acid.

“Although the survey was not designed to correlate skin care practices with wound culture results and resistance patterns, widespread use of topical antimicrobials described among EB patients highlights the need for increased emphasis on antibiotic stewardship,” the researchers noted. They added that health care providers should educate patients and families not only about mindful use of antibiotics, but also appropriate concentrations of cleansing additives.

“Optimizing EB patient home skin care routines, along with future longitudinal studies on the impact of EB skin care interventions on microbial resistance patterns, wound healing and [squamous cell carcinoma] risk are necessary to improve outcomes for patients with EB,” they emphasized.

The Epidermolysis Bullosa Clinical Characterization and Outcomes Database used in the study is funded by the Epidermolysis Bullosa Research Partnership and the Epidermolysis Bullosa Medical Research Foundation. Ms. Shayegan had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies including Abeona Therapeutics, Castle Creek Pharmaceuticals, Fibrocell Science, ProQR, and Scioderm.

SOURCE: Shayegan L et al. Pediatr Dermatol. 2020. doi: 10.1111/pde.14102.

Most patients with epidermolysis bullosa who use topical products choose antimicrobials, according to data from a survey of 202 children and adults.

Management of epidermolysis bullosa (EB) involves a combination of skin protection and infection management, but patient home care practices have not been well studied, wrote Leila Shayegan of Columbia University, New York, and colleagues.

In a study published in Pediatric Dermatology, the researchers surveyed 202 patients who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database during 2017. The patients ranged in age from 1 month to 62 years with an average age of 11 years; 52% were female. The patients represented a range of EB subtypes, including 130 patients with dystrophic EB, 51 patients with EB simplex, 21 with junctional EB, and 3 patients each with Kindler syndrome and unspecified subtypes.

Overall, most of the patients reported cleaning their skin either every day (37%) or every other day (32%). Of the 188 patients who reported using topical products on their wounds, 131 (70%) said they used at least one antimicrobial product, while 125 patients (66%) reported using at least one emollient; 32 (17%) used emollients only, and 21(11%) reported no use of topical products.

The most popular topical antibiotics were mupirocin (31%) and bacitracin (31%). In addition, 14% of respondents used silver-containing products, and 16% used medical-grade honey. Roughly half (51%) of patients who reported use of at least one antimicrobial product used two or more different antimicrobial products.

A total of 38% of patients used only water for cleansing. Of the 131 patients who reported using additives in their cleansing water, 57% added salt, 54% added bleach, 27% added vinegar, and 26% reported “other” additive use, which could include Epsom salt, baking soda, oatmeal, or essential oils, the researchers said. The concentrations of these additives ranged from barely effective 0.002% sodium hypochlorite and 0.002% acetic acid solutions to potentially cytotoxic solutions of 0.09% sodium hypochlorite and 0.156% acetic acid.

“Although the survey was not designed to correlate skin care practices with wound culture results and resistance patterns, widespread use of topical antimicrobials described among EB patients highlights the need for increased emphasis on antibiotic stewardship,” the researchers noted. They added that health care providers should educate patients and families not only about mindful use of antibiotics, but also appropriate concentrations of cleansing additives.

“Optimizing EB patient home skin care routines, along with future longitudinal studies on the impact of EB skin care interventions on microbial resistance patterns, wound healing and [squamous cell carcinoma] risk are necessary to improve outcomes for patients with EB,” they emphasized.

The Epidermolysis Bullosa Clinical Characterization and Outcomes Database used in the study is funded by the Epidermolysis Bullosa Research Partnership and the Epidermolysis Bullosa Medical Research Foundation. Ms. Shayegan had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies including Abeona Therapeutics, Castle Creek Pharmaceuticals, Fibrocell Science, ProQR, and Scioderm.

SOURCE: Shayegan L et al. Pediatr Dermatol. 2020. doi: 10.1111/pde.14102.

The Food and Drug Administration has approved the first drug to combat peanut allergy in children, (Palforzia, Aimmune Therapeutics), although those who take it must continue to avoid peanuts in their diets.

The peanut (Arachis hypogaea) allergen powder is also the first drug ever approved to treat a food allergy. It is not a cure, but it mitigates allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts, the FDA said in a news release.

Treatment with the oral powder, which is mixed into semisolid food – such as applesauce or yogurt – can be started in children aged 4 through 17 years who have a confirmed peanut allergy and then continued as a maintenance medication. Some 1 million American children have peanut allergy, and only a fifth will outgrow the allergy, the agency said.

“Because there is no cure, allergic individuals must strictly avoid exposure to prevent severe and potentially life-threatening reactions,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement.

An FDA advisory panel backed the medication in September 2019, but some committee members expressed concern about the large number of children in clinical trials who required epinephrine after receiving a dose of Palforzia.

The initial dose phase is given on a single day, while updosing consists of 11 increasing doses over several months. If the patient tolerates the first administration of an increased dose level, they may continue that dose daily at home. Daily maintenance begins after the completion of all updosing levels.

The drug will carry a boxed warning on the risk of anaphylaxis with the drug, and the FDA is requiring a Risk Evaluation and Mitigation Strategy (REMS).

Palforzia will be available only through specially certified health care providers, health care settings, and pharmacies to patients enrolled in the REMS program, the agency said. Also, the initial dose escalation and first dose of each updosing level can be given only in a certified setting.

The agency said that patients or parents or caregivers must be counseled on the need for constant availability of injectable epinephrine, the need for continued dietary peanut avoidance, and on how to recognize the signs and symptoms of anaphylaxis.

‘Eagerly’ awaited

Palforzia’s effectiveness was based on a randomized, double-blind, placebo-controlled study involving about 500 peanut-allergic individuals that found that 67.2% of allergic patients tolerated an oral challenge with a single 600-mg dose of peanut protein with no more than mild allergic symptoms after 6 months of maintenance treatment, compared with 4% of placebo recipients, the FDA said.

In two double-blind, placebo-controlled studies looking at safety, the most commonly reported side effects among about 700 individuals involved in the research were abdominal pain, vomiting, nausea, tingling in the mouth, itching (including in the mouth and ears), cough, runny nose, throat irritation and tightness, hives, wheezing and shortness of breath, and anaphylaxis.

Palforzia should not be given to those with uncontrolled asthma and can’t be used for emergency treatment of allergic reactions, including anaphylaxis.

“The food allergy community has been eagerly awaiting an FDA-approved treatment that can help mitigate allergic reactions to peanut and, as allergists, we want nothing more than to have a treatment option to offer our patients that has demonstrated both the safety and efficacy to truly impact the lives of patients who live with peanut allergy,” said Christina Ciaccio, MD, chief of Allergy/Immunology and Pediatric Pulmonary Medicine at the University of Chicago Medical Center and Biological Sciences, in a company statement from Aimmune. “With today’s approval of Palforzia, we can – for the first time – offer children and teens with peanut allergy a proven medicine that employs an established therapeutic approach.”

This article first appeared on Medscape.com.

The Food and Drug Administration has approved the first drug to combat peanut allergy in children, (Palforzia, Aimmune Therapeutics), although those who take it must continue to avoid peanuts in their diets.

The peanut (Arachis hypogaea) allergen powder is also the first drug ever approved to treat a food allergy. It is not a cure, but it mitigates allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts, the FDA said in a news release.

Treatment with the oral powder, which is mixed into semisolid food – such as applesauce or yogurt – can be started in children aged 4 through 17 years who have a confirmed peanut allergy and then continued as a maintenance medication. Some 1 million American children have peanut allergy, and only a fifth will outgrow the allergy, the agency said.

“Because there is no cure, allergic individuals must strictly avoid exposure to prevent severe and potentially life-threatening reactions,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement.

An FDA advisory panel backed the medication in September 2019, but some committee members expressed concern about the large number of children in clinical trials who required epinephrine after receiving a dose of Palforzia.

The initial dose phase is given on a single day, while updosing consists of 11 increasing doses over several months. If the patient tolerates the first administration of an increased dose level, they may continue that dose daily at home. Daily maintenance begins after the completion of all updosing levels.

The drug will carry a boxed warning on the risk of anaphylaxis with the drug, and the FDA is requiring a Risk Evaluation and Mitigation Strategy (REMS).

Palforzia will be available only through specially certified health care providers, health care settings, and pharmacies to patients enrolled in the REMS program, the agency said. Also, the initial dose escalation and first dose of each updosing level can be given only in a certified setting.

The agency said that patients or parents or caregivers must be counseled on the need for constant availability of injectable epinephrine, the need for continued dietary peanut avoidance, and on how to recognize the signs and symptoms of anaphylaxis.

‘Eagerly’ awaited

Palforzia’s effectiveness was based on a randomized, double-blind, placebo-controlled study involving about 500 peanut-allergic individuals that found that 67.2% of allergic patients tolerated an oral challenge with a single 600-mg dose of peanut protein with no more than mild allergic symptoms after 6 months of maintenance treatment, compared with 4% of placebo recipients, the FDA said.

In two double-blind, placebo-controlled studies looking at safety, the most commonly reported side effects among about 700 individuals involved in the research were abdominal pain, vomiting, nausea, tingling in the mouth, itching (including in the mouth and ears), cough, runny nose, throat irritation and tightness, hives, wheezing and shortness of breath, and anaphylaxis.

Palforzia should not be given to those with uncontrolled asthma and can’t be used for emergency treatment of allergic reactions, including anaphylaxis.

“The food allergy community has been eagerly awaiting an FDA-approved treatment that can help mitigate allergic reactions to peanut and, as allergists, we want nothing more than to have a treatment option to offer our patients that has demonstrated both the safety and efficacy to truly impact the lives of patients who live with peanut allergy,” said Christina Ciaccio, MD, chief of Allergy/Immunology and Pediatric Pulmonary Medicine at the University of Chicago Medical Center and Biological Sciences, in a company statement from Aimmune. “With today’s approval of Palforzia, we can – for the first time – offer children and teens with peanut allergy a proven medicine that employs an established therapeutic approach.”

This article first appeared on Medscape.com.

The Food and Drug Administration has approved the first drug to combat peanut allergy in children, (Palforzia, Aimmune Therapeutics), although those who take it must continue to avoid peanuts in their diets.

The peanut (Arachis hypogaea) allergen powder is also the first drug ever approved to treat a food allergy. It is not a cure, but it mitigates allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts, the FDA said in a news release.

Treatment with the oral powder, which is mixed into semisolid food – such as applesauce or yogurt – can be started in children aged 4 through 17 years who have a confirmed peanut allergy and then continued as a maintenance medication. Some 1 million American children have peanut allergy, and only a fifth will outgrow the allergy, the agency said.

“Because there is no cure, allergic individuals must strictly avoid exposure to prevent severe and potentially life-threatening reactions,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement.

An FDA advisory panel backed the medication in September 2019, but some committee members expressed concern about the large number of children in clinical trials who required epinephrine after receiving a dose of Palforzia.

The initial dose phase is given on a single day, while updosing consists of 11 increasing doses over several months. If the patient tolerates the first administration of an increased dose level, they may continue that dose daily at home. Daily maintenance begins after the completion of all updosing levels.

The drug will carry a boxed warning on the risk of anaphylaxis with the drug, and the FDA is requiring a Risk Evaluation and Mitigation Strategy (REMS).

Palforzia will be available only through specially certified health care providers, health care settings, and pharmacies to patients enrolled in the REMS program, the agency said. Also, the initial dose escalation and first dose of each updosing level can be given only in a certified setting.

The agency said that patients or parents or caregivers must be counseled on the need for constant availability of injectable epinephrine, the need for continued dietary peanut avoidance, and on how to recognize the signs and symptoms of anaphylaxis.

‘Eagerly’ awaited

Palforzia’s effectiveness was based on a randomized, double-blind, placebo-controlled study involving about 500 peanut-allergic individuals that found that 67.2% of allergic patients tolerated an oral challenge with a single 600-mg dose of peanut protein with no more than mild allergic symptoms after 6 months of maintenance treatment, compared with 4% of placebo recipients, the FDA said.

In two double-blind, placebo-controlled studies looking at safety, the most commonly reported side effects among about 700 individuals involved in the research were abdominal pain, vomiting, nausea, tingling in the mouth, itching (including in the mouth and ears), cough, runny nose, throat irritation and tightness, hives, wheezing and shortness of breath, and anaphylaxis.

Palforzia should not be given to those with uncontrolled asthma and can’t be used for emergency treatment of allergic reactions, including anaphylaxis.

“The food allergy community has been eagerly awaiting an FDA-approved treatment that can help mitigate allergic reactions to peanut and, as allergists, we want nothing more than to have a treatment option to offer our patients that has demonstrated both the safety and efficacy to truly impact the lives of patients who live with peanut allergy,” said Christina Ciaccio, MD, chief of Allergy/Immunology and Pediatric Pulmonary Medicine at the University of Chicago Medical Center and Biological Sciences, in a company statement from Aimmune. “With today’s approval of Palforzia, we can – for the first time – offer children and teens with peanut allergy a proven medicine that employs an established therapeutic approach.”

This article first appeared on Medscape.com.

BALTIMORE – About one in 4,000 children are born with hemimegalencephaly, meaning one brain hemisphere is abnormally formed and larger than the other.

The abnormal hemisphere causes seizures, and when they become intractable, the standard of care is to remove it as soon as possible; the longer the abnormal hemisphere is left in, the worse children do developmentally, and the less likely hemispherectomy will stop the seizures.

A problem comes up, however, when children become intractable before they’re 3 months old: “Neurosurgeons won’t touch them,” said Taeun Chang, MD, a neonatal neurointensivist at Children’s National Medical Center in Washington.

Newborns’ coagulation systems aren’t fully developed, and the risk of fatal hemorrhage is too high, she explained.

Out of what she said was a sense of “desperation” to address the situation, Dr. Chang has spearheaded a new approach for newborns at Children’s National, serial glue embolization to induce targeted strokes in the affected hemisphere. She reported on the first five cases at the American Epilepsy Society annual meeting.

At this point, “I feel like we’ve pretty much figured out the technique in terms of minimizing the complications. There’s no reason to wait anymore” for surgery as newborns get worse and worse, she said.

The technique

In two or three stages over several days, the major branches of the affected hemisphere’s anterior, middle, and posterior cerebral arteries are embolized. “You have to glue a long area and put in a lot of glue and glue up the secondary branches because [newborns] are so good at forming collaterals,” Dr. Chang said.

Fresh frozen plasma is given before and after each embolization session to boost coagulation proteins. Nicardipine is given during the procedure to prevent vasospasms. The one death in the series, case four, was in an 11-day old girl who vasospasmed, ruptured an artery over the tip of the guidewire, and hemorrhaged.

After the procedure, body temperature is kept at 36° C to prevent fever; sodium is kept high, and ins and outs are matched, to reduce brain edema; and blood pressure is tightly controlled. Children are kept on EEG during embolization and for days afterwards, and seizures, if any, are treated. The next embolization comes after peak swelling has passed in about 48-72 hours.

“The reason we can get away with this without herniation is that newborns’ skulls are soft, and their sutures are open,” so cerebral edema is manageable, Dr. Chang said.

Learning curve and outcomes

“What we learned in the first two cases” – a 23-day-old boy and 49-day-old girl – “was to create effective strokes. That’s not something any of us are taught to do,” she said.

“We were not trying to destroy the whole hemisphere, just the area that was seizing on EEG.” That was a mistake, she said: Adjacent areas began seizing and both children went on to anatomical hemispherectomies and needed shunts.

They are 5 years old now, and both on four seizure medications. The boy is in a wheelchair, fed by a G-tube, and has fewer than 20 words. The girl has a gait trainer, is fed mostly by G-tube, and has more than 50 words.

The third patient had her middle and posterior cerebral arteries embolized beginning when she was 43 days old. She was seizure free when she left the NICU, but eventually had a functional hemispherectomy. She’s 2 years old now, eating by mouth, in a gait trainer, and speaks in one- or two-word sentences. She’s on three seizure medications.

Outcomes have been best for patient five. Her posterior, middle, and anterior cerebral arteries were embolized starting at 14 days. She’s 1 year old now, seizure free on three medications, eating by G-tube and mouth, and has three-five words.

Dr. Chang said that newborns with hemimegalencephaly at Children’s National aren’t lingering as long on failing drug regimens these days. “We go to intervention now that we have this option” after they fail just two or three medications.

Given that the fifth patient, treated at 2 weeks old, is the only one who has been seizure free, she suspects it’s probably best to do embolization sooner rather than later, just as with anatomical hemispherectomy in older children. “We’ve got the sense that even a couple of weeks makes a difference. People need to come to us sooner,” Dr. Chang said.

It’s possible embolization could be a sound alternative to surgery even after 3 months of age. Focal embolization might also be a viable alternative to surgery to knock out epileptogenic lesions in children with tuberous sclerosis. Dr. Chang and her colleagues are interested in those and other possibilities, and plan to continue to develop the approach, she said.

There was no funding, and the investigators didn’t have any relevant disclosures.

[email protected]

SOURCE: Chang T et al. AES 2019, Abstract 1.225.

BALTIMORE – About one in 4,000 children are born with hemimegalencephaly, meaning one brain hemisphere is abnormally formed and larger than the other.

The abnormal hemisphere causes seizures, and when they become intractable, the standard of care is to remove it as soon as possible; the longer the abnormal hemisphere is left in, the worse children do developmentally, and the less likely hemispherectomy will stop the seizures.

A problem comes up, however, when children become intractable before they’re 3 months old: “Neurosurgeons won’t touch them,” said Taeun Chang, MD, a neonatal neurointensivist at Children’s National Medical Center in Washington.

Newborns’ coagulation systems aren’t fully developed, and the risk of fatal hemorrhage is too high, she explained.

Out of what she said was a sense of “desperation” to address the situation, Dr. Chang has spearheaded a new approach for newborns at Children’s National, serial glue embolization to induce targeted strokes in the affected hemisphere. She reported on the first five cases at the American Epilepsy Society annual meeting.

At this point, “I feel like we’ve pretty much figured out the technique in terms of minimizing the complications. There’s no reason to wait anymore” for surgery as newborns get worse and worse, she said.

The technique

In two or three stages over several days, the major branches of the affected hemisphere’s anterior, middle, and posterior cerebral arteries are embolized. “You have to glue a long area and put in a lot of glue and glue up the secondary branches because [newborns] are so good at forming collaterals,” Dr. Chang said.

Fresh frozen plasma is given before and after each embolization session to boost coagulation proteins. Nicardipine is given during the procedure to prevent vasospasms. The one death in the series, case four, was in an 11-day old girl who vasospasmed, ruptured an artery over the tip of the guidewire, and hemorrhaged.

After the procedure, body temperature is kept at 36° C to prevent fever; sodium is kept high, and ins and outs are matched, to reduce brain edema; and blood pressure is tightly controlled. Children are kept on EEG during embolization and for days afterwards, and seizures, if any, are treated. The next embolization comes after peak swelling has passed in about 48-72 hours.

“The reason we can get away with this without herniation is that newborns’ skulls are soft, and their sutures are open,” so cerebral edema is manageable, Dr. Chang said.

Learning curve and outcomes

“What we learned in the first two cases” – a 23-day-old boy and 49-day-old girl – “was to create effective strokes. That’s not something any of us are taught to do,” she said.

“We were not trying to destroy the whole hemisphere, just the area that was seizing on EEG.” That was a mistake, she said: Adjacent areas began seizing and both children went on to anatomical hemispherectomies and needed shunts.

They are 5 years old now, and both on four seizure medications. The boy is in a wheelchair, fed by a G-tube, and has fewer than 20 words. The girl has a gait trainer, is fed mostly by G-tube, and has more than 50 words.

The third patient had her middle and posterior cerebral arteries embolized beginning when she was 43 days old. She was seizure free when she left the NICU, but eventually had a functional hemispherectomy. She’s 2 years old now, eating by mouth, in a gait trainer, and speaks in one- or two-word sentences. She’s on three seizure medications.

Outcomes have been best for patient five. Her posterior, middle, and anterior cerebral arteries were embolized starting at 14 days. She’s 1 year old now, seizure free on three medications, eating by G-tube and mouth, and has three-five words.

Dr. Chang said that newborns with hemimegalencephaly at Children’s National aren’t lingering as long on failing drug regimens these days. “We go to intervention now that we have this option” after they fail just two or three medications.

Given that the fifth patient, treated at 2 weeks old, is the only one who has been seizure free, she suspects it’s probably best to do embolization sooner rather than later, just as with anatomical hemispherectomy in older children. “We’ve got the sense that even a couple of weeks makes a difference. People need to come to us sooner,” Dr. Chang said.

It’s possible embolization could be a sound alternative to surgery even after 3 months of age. Focal embolization might also be a viable alternative to surgery to knock out epileptogenic lesions in children with tuberous sclerosis. Dr. Chang and her colleagues are interested in those and other possibilities, and plan to continue to develop the approach, she said.

There was no funding, and the investigators didn’t have any relevant disclosures.

[email protected]

SOURCE: Chang T et al. AES 2019, Abstract 1.225.

BALTIMORE – About one in 4,000 children are born with hemimegalencephaly, meaning one brain hemisphere is abnormally formed and larger than the other.

The abnormal hemisphere causes seizures, and when they become intractable, the standard of care is to remove it as soon as possible; the longer the abnormal hemisphere is left in, the worse children do developmentally, and the less likely hemispherectomy will stop the seizures.

A problem comes up, however, when children become intractable before they’re 3 months old: “Neurosurgeons won’t touch them,” said Taeun Chang, MD, a neonatal neurointensivist at Children’s National Medical Center in Washington.

Newborns’ coagulation systems aren’t fully developed, and the risk of fatal hemorrhage is too high, she explained.

Out of what she said was a sense of “desperation” to address the situation, Dr. Chang has spearheaded a new approach for newborns at Children’s National, serial glue embolization to induce targeted strokes in the affected hemisphere. She reported on the first five cases at the American Epilepsy Society annual meeting.

At this point, “I feel like we’ve pretty much figured out the technique in terms of minimizing the complications. There’s no reason to wait anymore” for surgery as newborns get worse and worse, she said.

The technique

In two or three stages over several days, the major branches of the affected hemisphere’s anterior, middle, and posterior cerebral arteries are embolized. “You have to glue a long area and put in a lot of glue and glue up the secondary branches because [newborns] are so good at forming collaterals,” Dr. Chang said.

Fresh frozen plasma is given before and after each embolization session to boost coagulation proteins. Nicardipine is given during the procedure to prevent vasospasms. The one death in the series, case four, was in an 11-day old girl who vasospasmed, ruptured an artery over the tip of the guidewire, and hemorrhaged.

After the procedure, body temperature is kept at 36° C to prevent fever; sodium is kept high, and ins and outs are matched, to reduce brain edema; and blood pressure is tightly controlled. Children are kept on EEG during embolization and for days afterwards, and seizures, if any, are treated. The next embolization comes after peak swelling has passed in about 48-72 hours.

“The reason we can get away with this without herniation is that newborns’ skulls are soft, and their sutures are open,” so cerebral edema is manageable, Dr. Chang said.

Learning curve and outcomes

“What we learned in the first two cases” – a 23-day-old boy and 49-day-old girl – “was to create effective strokes. That’s not something any of us are taught to do,” she said.

“We were not trying to destroy the whole hemisphere, just the area that was seizing on EEG.” That was a mistake, she said: Adjacent areas began seizing and both children went on to anatomical hemispherectomies and needed shunts.

They are 5 years old now, and both on four seizure medications. The boy is in a wheelchair, fed by a G-tube, and has fewer than 20 words. The girl has a gait trainer, is fed mostly by G-tube, and has more than 50 words.

The third patient had her middle and posterior cerebral arteries embolized beginning when she was 43 days old. She was seizure free when she left the NICU, but eventually had a functional hemispherectomy. She’s 2 years old now, eating by mouth, in a gait trainer, and speaks in one- or two-word sentences. She’s on three seizure medications.

Outcomes have been best for patient five. Her posterior, middle, and anterior cerebral arteries were embolized starting at 14 days. She’s 1 year old now, seizure free on three medications, eating by G-tube and mouth, and has three-five words.

Dr. Chang said that newborns with hemimegalencephaly at Children’s National aren’t lingering as long on failing drug regimens these days. “We go to intervention now that we have this option” after they fail just two or three medications.

Given that the fifth patient, treated at 2 weeks old, is the only one who has been seizure free, she suspects it’s probably best to do embolization sooner rather than later, just as with anatomical hemispherectomy in older children. “We’ve got the sense that even a couple of weeks makes a difference. People need to come to us sooner,” Dr. Chang said.

It’s possible embolization could be a sound alternative to surgery even after 3 months of age. Focal embolization might also be a viable alternative to surgery to knock out epileptogenic lesions in children with tuberous sclerosis. Dr. Chang and her colleagues are interested in those and other possibilities, and plan to continue to develop the approach, she said.

There was no funding, and the investigators didn’t have any relevant disclosures.

[email protected]

SOURCE: Chang T et al. AES 2019, Abstract 1.225.

ORLANDO – Because Food and Drug Administration–approved treatment options for children and adolescents with severe dermatologic diseases are limited, systemic therapies for these patients often require the use of off-label medications. However, this scenario is changing, A. Yasmine Kirkorian, MD, said at the ODAC Dermatology, Aesthetic & Surgical Conference.

Jeff Craven/MDedge News

“I really would like to emphasize that children with severe disease need to be treated,” added Dr. Kirkorian, a pediatric dermatologist at George Washington University, Washington, and Children’s National Health System, where she is interim chief of the division of dermatology.

Current on-label systemic therapies for pediatric skin disease include etanercept for psoriasis (4 years and older), ustekinumab for psoriasis (12 years and older), adalimumab for hidradenitis suppurativa (12 years and older), and omalizumab for chronic idiopathic urticaria (12 years and older). A new addition to the list is dupilumab, which was approved for children and adolescents with atopic dermatitis (AD) aged 12 years and older in 2019, she noted.

Dupilumab is currently being studied in children aged 6 months to 12 years, and other clinical trials are evaluating more options for pediatric patients with AD, alopecia areata, and psoriasis. They include a clinical trial of the oral Janus kinase 3 (JAK3) inhibitor PF-06651600 in patients aged 12 years and older with alopecia areata. Six biologic therapies are being evaluated for psoriasis in patients beginning at 6 years: ixekizumab, secukinumab, ustekinumab, guselkumab, brodalumab, and apremilast.

Some systemic therapies are off-label “but used all the time” for dermatologic diseases in pediatrics, Dr. Kirkorian noted. One example is methotrexate, which is approved by the FDA for acute lymphoblastic leukemia, meningeal leukemia, and juvenile idiopathic arthritis down to infancy. Having existing efficacy and safety data for a medication in a pediatric population, even for a different disease, can be helpful when counseling parents of children with severe dermatologic disease. “If you have something, even in an older population of children, it can be reassuring, or you can use evidence from other diseases,” she said.

While methotrexate is a cheap option and approved by the FDA for other pediatric indications down to infancy, the cons of using it to treat AD in pediatric patients are numerous. Treatment requires a number of blood draws for lab testing, which can be discouraging for younger patients, and the reported adverse effect profile may be concerning to some parents, while “in practice doesn’t really occur,” she said. Methotrexate is a teratogen so is not appropriate for teenagers who are sexually active and not using contraception.

The “biggest problem,” though, is the issue of whether methotrexate is effective, since it doesn’t always work for AD, Dr. Kirkorian said. “Even at the highest doses, I often feel that we fail the atopic children,” as opposed to using it to treat psoriasis, “where you know I’m going to get you on something that works.”

In contrast, cyclosporine is FDA approved down to infancy, and works quickly as a bridge to other therapy, and is not expensive, Dr. Kirkorian said. Cons include the need for blood draws, blood pressure checks, drug interactions, and adverse effects, she noted, adding that she tries to use cyclosporine as a bridge to on-label and off-label dupilumab.

Even with FDA approval for dupilumab down to age 12 years, she said it can be difficult to get insurance approval for the on-label treatment for patients in this age group with AD, before they first fail other therapies (even with off-label systemic drugs). For patients under age 12 years, getting approval is even more challenging and requires rigorous documentation of what therapies the child has failed, and how it has affected their quality of life, she said.

“If you send in a letter to the insurance company without an IGA [Investigator Global Assessment] or SCORAD, you’re going to get rejected,” Dr. Kirkorian said. In addition to those two measures, she provides “everything else,” including the impact of the disease on quality of life of patients, and school, she said, adding, “Did they miss school, did they get hospitalized for infections? And do they have comorbid diseases that might help you get approval?”

In pediatric patients with psoriasis, common issues are more likely to be about how insurance dictates step therapy. She has often found that young children may stop responding to etanercept after a few years, which can justify a switch to ustekinumab or a new treatment in a clinical trial, she said. Adolescents with psoriasis can receive ustekinumab, which is approved for psoriasis in patients aged 12-17 years, she said, noting that the infrequent ustekinumab dosing schedule is often beneficial in this population.

When all other approved options fail for young patients with psoriasis, justifying off-label use isn’t always easy. “You just have to make a justification based on the literature, even though it’s off label,” citing available safety information for other diseases, and “demonstrate over and over the impact on quality of life,” which works “most of the time,” Dr. Kirkorian said.

She reported having no conflicts of interest.

ORLANDO – Because Food and Drug Administration–approved treatment options for children and adolescents with severe dermatologic diseases are limited, systemic therapies for these patients often require the use of off-label medications. However, this scenario is changing, A. Yasmine Kirkorian, MD, said at the ODAC Dermatology, Aesthetic & Surgical Conference.

Jeff Craven/MDedge News

“I really would like to emphasize that children with severe disease need to be treated,” added Dr. Kirkorian, a pediatric dermatologist at George Washington University, Washington, and Children’s National Health System, where she is interim chief of the division of dermatology.

Current on-label systemic therapies for pediatric skin disease include etanercept for psoriasis (4 years and older), ustekinumab for psoriasis (12 years and older), adalimumab for hidradenitis suppurativa (12 years and older), and omalizumab for chronic idiopathic urticaria (12 years and older). A new addition to the list is dupilumab, which was approved for children and adolescents with atopic dermatitis (AD) aged 12 years and older in 2019, she noted.

Dupilumab is currently being studied in children aged 6 months to 12 years, and other clinical trials are evaluating more options for pediatric patients with AD, alopecia areata, and psoriasis. They include a clinical trial of the oral Janus kinase 3 (JAK3) inhibitor PF-06651600 in patients aged 12 years and older with alopecia areata. Six biologic therapies are being evaluated for psoriasis in patients beginning at 6 years: ixekizumab, secukinumab, ustekinumab, guselkumab, brodalumab, and apremilast.

Some systemic therapies are off-label “but used all the time” for dermatologic diseases in pediatrics, Dr. Kirkorian noted. One example is methotrexate, which is approved by the FDA for acute lymphoblastic leukemia, meningeal leukemia, and juvenile idiopathic arthritis down to infancy. Having existing efficacy and safety data for a medication in a pediatric population, even for a different disease, can be helpful when counseling parents of children with severe dermatologic disease. “If you have something, even in an older population of children, it can be reassuring, or you can use evidence from other diseases,” she said.

While methotrexate is a cheap option and approved by the FDA for other pediatric indications down to infancy, the cons of using it to treat AD in pediatric patients are numerous. Treatment requires a number of blood draws for lab testing, which can be discouraging for younger patients, and the reported adverse effect profile may be concerning to some parents, while “in practice doesn’t really occur,” she said. Methotrexate is a teratogen so is not appropriate for teenagers who are sexually active and not using contraception.

The “biggest problem,” though, is the issue of whether methotrexate is effective, since it doesn’t always work for AD, Dr. Kirkorian said. “Even at the highest doses, I often feel that we fail the atopic children,” as opposed to using it to treat psoriasis, “where you know I’m going to get you on something that works.”

In contrast, cyclosporine is FDA approved down to infancy, and works quickly as a bridge to other therapy, and is not expensive, Dr. Kirkorian said. Cons include the need for blood draws, blood pressure checks, drug interactions, and adverse effects, she noted, adding that she tries to use cyclosporine as a bridge to on-label and off-label dupilumab.

Even with FDA approval for dupilumab down to age 12 years, she said it can be difficult to get insurance approval for the on-label treatment for patients in this age group with AD, before they first fail other therapies (even with off-label systemic drugs). For patients under age 12 years, getting approval is even more challenging and requires rigorous documentation of what therapies the child has failed, and how it has affected their quality of life, she said.

“If you send in a letter to the insurance company without an IGA [Investigator Global Assessment] or SCORAD, you’re going to get rejected,” Dr. Kirkorian said. In addition to those two measures, she provides “everything else,” including the impact of the disease on quality of life of patients, and school, she said, adding, “Did they miss school, did they get hospitalized for infections? And do they have comorbid diseases that might help you get approval?”

In pediatric patients with psoriasis, common issues are more likely to be about how insurance dictates step therapy. She has often found that young children may stop responding to etanercept after a few years, which can justify a switch to ustekinumab or a new treatment in a clinical trial, she said. Adolescents with psoriasis can receive ustekinumab, which is approved for psoriasis in patients aged 12-17 years, she said, noting that the infrequent ustekinumab dosing schedule is often beneficial in this population.

When all other approved options fail for young patients with psoriasis, justifying off-label use isn’t always easy. “You just have to make a justification based on the literature, even though it’s off label,” citing available safety information for other diseases, and “demonstrate over and over the impact on quality of life,” which works “most of the time,” Dr. Kirkorian said.

She reported having no conflicts of interest.

ORLANDO – Because Food and Drug Administration–approved treatment options for children and adolescents with severe dermatologic diseases are limited, systemic therapies for these patients often require the use of off-label medications. However, this scenario is changing, A. Yasmine Kirkorian, MD, said at the ODAC Dermatology, Aesthetic & Surgical Conference.

Jeff Craven/MDedge News

“I really would like to emphasize that children with severe disease need to be treated,” added Dr. Kirkorian, a pediatric dermatologist at George Washington University, Washington, and Children’s National Health System, where she is interim chief of the division of dermatology.

Current on-label systemic therapies for pediatric skin disease include etanercept for psoriasis (4 years and older), ustekinumab for psoriasis (12 years and older), adalimumab for hidradenitis suppurativa (12 years and older), and omalizumab for chronic idiopathic urticaria (12 years and older). A new addition to the list is dupilumab, which was approved for children and adolescents with atopic dermatitis (AD) aged 12 years and older in 2019, she noted.

Dupilumab is currently being studied in children aged 6 months to 12 years, and other clinical trials are evaluating more options for pediatric patients with AD, alopecia areata, and psoriasis. They include a clinical trial of the oral Janus kinase 3 (JAK3) inhibitor PF-06651600 in patients aged 12 years and older with alopecia areata. Six biologic therapies are being evaluated for psoriasis in patients beginning at 6 years: ixekizumab, secukinumab, ustekinumab, guselkumab, brodalumab, and apremilast.

Some systemic therapies are off-label “but used all the time” for dermatologic diseases in pediatrics, Dr. Kirkorian noted. One example is methotrexate, which is approved by the FDA for acute lymphoblastic leukemia, meningeal leukemia, and juvenile idiopathic arthritis down to infancy. Having existing efficacy and safety data for a medication in a pediatric population, even for a different disease, can be helpful when counseling parents of children with severe dermatologic disease. “If you have something, even in an older population of children, it can be reassuring, or you can use evidence from other diseases,” she said.

While methotrexate is a cheap option and approved by the FDA for other pediatric indications down to infancy, the cons of using it to treat AD in pediatric patients are numerous. Treatment requires a number of blood draws for lab testing, which can be discouraging for younger patients, and the reported adverse effect profile may be concerning to some parents, while “in practice doesn’t really occur,” she said. Methotrexate is a teratogen so is not appropriate for teenagers who are sexually active and not using contraception.

The “biggest problem,” though, is the issue of whether methotrexate is effective, since it doesn’t always work for AD, Dr. Kirkorian said. “Even at the highest doses, I often feel that we fail the atopic children,” as opposed to using it to treat psoriasis, “where you know I’m going to get you on something that works.”

In contrast, cyclosporine is FDA approved down to infancy, and works quickly as a bridge to other therapy, and is not expensive, Dr. Kirkorian said. Cons include the need for blood draws, blood pressure checks, drug interactions, and adverse effects, she noted, adding that she tries to use cyclosporine as a bridge to on-label and off-label dupilumab.

Even with FDA approval for dupilumab down to age 12 years, she said it can be difficult to get insurance approval for the on-label treatment for patients in this age group with AD, before they first fail other therapies (even with off-label systemic drugs). For patients under age 12 years, getting approval is even more challenging and requires rigorous documentation of what therapies the child has failed, and how it has affected their quality of life, she said.

“If you send in a letter to the insurance company without an IGA [Investigator Global Assessment] or SCORAD, you’re going to get rejected,” Dr. Kirkorian said. In addition to those two measures, she provides “everything else,” including the impact of the disease on quality of life of patients, and school, she said, adding, “Did they miss school, did they get hospitalized for infections? And do they have comorbid diseases that might help you get approval?”

In pediatric patients with psoriasis, common issues are more likely to be about how insurance dictates step therapy. She has often found that young children may stop responding to etanercept after a few years, which can justify a switch to ustekinumab or a new treatment in a clinical trial, she said. Adolescents with psoriasis can receive ustekinumab, which is approved for psoriasis in patients aged 12-17 years, she said, noting that the infrequent ustekinumab dosing schedule is often beneficial in this population.

When all other approved options fail for young patients with psoriasis, justifying off-label use isn’t always easy. “You just have to make a justification based on the literature, even though it’s off label,” citing available safety information for other diseases, and “demonstrate over and over the impact on quality of life,” which works “most of the time,” Dr. Kirkorian said.

She reported having no conflicts of interest.

NEW ORLEANS – With more than 10% of children receiving complementary or alternative medicine (CAM), you should be familiar with what does and doesn’t work when it comes to using supplements for various medical issues, said Cora Breuner, MD, a professor of pediatrics at the University of Washington, Seattle, and attending physician at Seattle Children’s Hospital.

Dr. Breuner presented an overview of more than a dozen popular supplements with their uses and evidence at the American Academy of Pediatrics annual meeting. Most of the evidence comes from studies in adults, not children, and the evidence overall is sometimes scant, but it can guide physicians in discussing options with parents interested in CAM.
 

Butterbur

This root primarily is used to treat migraines via anti-inflammatory effects. The ideal dose is 50-75 mg daily in 2-3 divided doses for children aged 8-9 years and 100-150 mg daily in 2-3 divided doses for those aged 10 and older (Headache. 2005 Mar;45:196-203; Eur J Pain. 2008;12:301-13; Neurology. 2012 Apr 24;78[17]:1346-53).

Adverse effects are mostly gastrointestinal, such as diarrhea and stomach upset, and dermal/allergic reactions, such as itchy eyes, asthma, and itching.
 

Caffeine

Caffeine is the most popular drug of choice for reducing drowsiness and increasing alertness and has the strongest evidence base, including for improving sports and work performance (J Strength Cond Res. 2010 Jan;24[1]:257-65). Regular caffeine use can lead to dependence, however, and it can cause anxiety, nervousness, irritability, insomnia, peptic ulcers, palpitations, gastroesophageal reflux disease (GERD), and tremors. Withdrawal can involve headaches, irritability, and anxiety.

Cannabidiol

Marijuana has more than 80 cannabinoids, and a nonpsychoactive one, cannabidiol, makes up about 40% of cannabis extracts, Dr. Breuner said. It’s been used as an anticonvulsant and to combat anxiety, psychosis, nausea and rheumatoid arthritis pain. In a study using a rat model for arthritis, inflammation and pain-related behaviors decreased in rats that received cannabidiol (Eur J Pain. 2016 Jul;20[6]:936-48).

A human dose would be about 160-300 mg daily, but side effects can include dry mouth, hypotension, lightheadedness, psychomotor slowing, sedation, and sleepiness.
 

Coenzyme Q10

This antioxidant is fat-soluble and has a chemical structure similar to vitamin K. It has been used in people with autism, chronic fatigue syndrome, fatigue from chemotherapy, Lyme disease, and muscular dystrophy, but the evidence focuses on fibromyalgia. One study of patients with fibromyalgia found that a 300-mg daily dose for 40 days reduced pain by 52%-56%, fatigue by 47%, morning tiredness by 56%, and tender points by 44%, compared with baseline (Antioxid Redox Signal. 2013;19[12]:1356-61.)

In another, 200 mg of coenzyme Q10 with 200 mg ginkgo daily for 3 months resulted in improvement of quality of life measures, including physical fitness levels, emotional feelings, social activities, overall health, and pain (J Int Med Res. 2002;30:195-9).

Potential adverse effects of coenzyme Q10 include nausea, vomiting, diarrhea, appetite suppression, and heartburn, albeit typically in less than 1% of patients.
 

Echinacea

magicflute002/Thinkstock

Echinacea actually is approved in Germany for supportive therapy in treating upper respiratory tract infections, urogenital infections, and wound healing, Dr. Breuner said. Hypothesized mechanisms of action include stimulation of the alternate complement pathway, immune-modulating effects, activating nonspecific T cells, inhibiting viral replication, and enhancing phagocytosis.

However, in clinical studies, echinacea did not reduce the duration or severity of upper respiratory tract infections or the occurrence or severity of infection, compared with placebo (JAMA. 2003 Dec 3;290[21]:2824-30; N Engl J Med. 2005 Jul 28;353[4]:341-8); this was tested in children aged 2-11 years in the first study, and the mean age of the subjects in the second study was 21 years. A 2014 Cochrane review found no overall benefits for treating common colds but noted the possibility of “a weak benefit from some echinacea products” based on individual trials with consistently positive, yet nonsignificant, trends, albeit with “questionable clinical relevance” (Cochrane Database Syst Rev. 2014 Feb 20;[2]:CD000530).

People with autoimmune conditions or who are immunocompromised should not use echinacea.
 

Magnesium

Magnesium also is used to treat migraines with a dose of 300-500 mg daily, although also it can be consumed in food, such as soy beans, black beans, tofu, seeds, nuts, whole grains, and shellfish (Expert Rev Neurother. 2009 Mar;9[3]:369-79; Neurology. 2012 Apr 24;78[17]:1346-53).

Side effects can include diarrhea and interactions with bisphosphonates, antibiotics] and diuretics. Taking proton pump inhibitors also may reduce magnesium levels.
 

Melatonin

Wjeger/Thinkstockphotos

Melatonin, a synthetic version of the hormone produced in humans to signal the onset of nighttime, has been studied extensively for jet lag, insomnia, shift-work disorder, circadian rhythm disorders, and withdrawal from benzodiazepine and nicotine.

Research shows that melatonin can improve sleep onset, duration, and quality. Some research has shown increased total sleep time (PLoS One. 2013 May 17;8(5):e63773).

Some evidence suggests it has endocrine-disrupting adverse effects, such as inhibiting ovulation and impairing glucose utilization.
 

N-acetyl cysteine (NAC)

Although it’s primarily an antidote for acetaminophen and carbon monoxide poisoning, NAC has been used for a wide range of conditions, including reducing lipoprotein levels with hyperlipidemia and reducing risk of cardiovascular events in people with end-stage renal disease and other conditions. It also has been used in people with bipolar disorder, schizophrenia, PTSD, substance disorders, and Tourette syndrome.

“Some clinical research shows that taking NAC 900 mg daily for 4 weeks, followed by 900 mg twice daily for 4 weeks and then 900 mg three times daily for 4 weeks improves symptoms of irritability in children with autism,” Dr. Breuner said. Other research showed reduced irritability in children with autism when they took 1,200 mg of NAC daily with risperidone, compared with risperidone alone. One study also has found “that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents” (Iran J Psychiatry. 2017 Apr;12[2]:134-141).

Side effects can include diarrhea, nausea, and heartburn.
 

Omega-3 fatty acids: DHA and EHA

Docosahexanoic acid (DHA) and eicosapentanoic acid (EHA) have been used to treat ADHD, depression, heart disease, and also to lower the risk of macular degeneration.

A systematic review of 25 randomized controlled trials of more than 3,600 subjects found that “omega-3 supplementation generally correlated with improvements in blood biomarkers” (Nutrients. 2018 Aug 15;10[8]. pii: E1094). A small study in children with Tourette syndrome found that omega-3 fatty acids did not reduce tic scores, but “may be beneficial in reduction of tic-related impairment” for some children and teens (Pediatrics. 2012 Jun;129[6]:e1493-500).

Possible adverse effects include fishy taste, belching, nosebleeds, nausea, loose stools, and – at higher doses – decreased blood coagulation.
 

St. John’s wort

Alexandru Magurean/Thinkstock

This herb has long been used to treat depression and appears to work by inhibiting serotonin reuptake, monoamine oxidase (MAO), 5-hydroxytryptamine (5-HT), dopamine, noradrenaline, gamma aminobutyric acid (GABA), and glutamate. A 2005 Cochrane review found St. John’s wort to work better than placebo with similar effectiveness as standard antidepressants for mild to moderate depression, but its benefit for major depression is questionable (Cochrane Database Syst Rev. 2005 Apr 18;[2]:CD000448).

An ideal dose is 300 mg daily, but physicians should be aware of the herb’s potential for certain drug interactions. It may increase metabolism of warfarin, cyclosporin, HIV protease inhibitors, theophylline, digoxin, and oral contraceptives (Expert Opin Drug Metab Toxicol. 2012 Jun;8[6]:691-708). Other potential side effects include decreased platelet aggregation, serotonin syndrome, and photosensitivity.
 

Turmeric (curcumin)

SyedMirazurRahman/Thinkstock

Turmeric is an anti-inflammatory agent used for a wide range of complaints, but research primarily has focused on its use for pain. No studies exist in children, but a handful of studies have found reduction in joint pain and rheumatoid arthritis symptoms in adults with 500-mg doses twice daily (Phytother Res. 2012 Nov;26[11]:1719-25; J Med Food. 2017 Oct;20[10]:1022-30). One of these studies focused on a specific product, Instaflex, that contained turmeric among multiple other active ingredients (Nutr J. 2013 Nov 25;12[1]:154).

Potential adverse effects of turmeric/curcumin include constipation, dyspepsia, diarrhea, dissension, reflux, nausea, vomiting, itching, and hives.
 

Zinc

ilkab/Thinkstock

Like echinacea, zinc is commonly used to treat the common cold. A 2013 Cochrane review of randomized, controlled trials found that taking zinc “within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people, but some caution is needed due to the heterogeneity of the data” (Cochrane Database Syst Rev. 2013 Jun 18;[6]:CD001364). The dose is 75 mg a day, and potential adverse effects include bad taste, nausea, and anosmia.

Dr. Breuner said she had no relevant financial disclosures.

NEW ORLEANS – With more than 10% of children receiving complementary or alternative medicine (CAM), you should be familiar with what does and doesn’t work when it comes to using supplements for various medical issues, said Cora Breuner, MD, a professor of pediatrics at the University of Washington, Seattle, and attending physician at Seattle Children’s Hospital.

Dr. Breuner presented an overview of more than a dozen popular supplements with their uses and evidence at the American Academy of Pediatrics annual meeting. Most of the evidence comes from studies in adults, not children, and the evidence overall is sometimes scant, but it can guide physicians in discussing options with parents interested in CAM.
 

Butterbur

This root primarily is used to treat migraines via anti-inflammatory effects. The ideal dose is 50-75 mg daily in 2-3 divided doses for children aged 8-9 years and 100-150 mg daily in 2-3 divided doses for those aged 10 and older (Headache. 2005 Mar;45:196-203; Eur J Pain. 2008;12:301-13; Neurology. 2012 Apr 24;78[17]:1346-53).

Adverse effects are mostly gastrointestinal, such as diarrhea and stomach upset, and dermal/allergic reactions, such as itchy eyes, asthma, and itching.
 

Caffeine

Caffeine is the most popular drug of choice for reducing drowsiness and increasing alertness and has the strongest evidence base, including for improving sports and work performance (J Strength Cond Res. 2010 Jan;24[1]:257-65). Regular caffeine use can lead to dependence, however, and it can cause anxiety, nervousness, irritability, insomnia, peptic ulcers, palpitations, gastroesophageal reflux disease (GERD), and tremors. Withdrawal can involve headaches, irritability, and anxiety.

Cannabidiol

Marijuana has more than 80 cannabinoids, and a nonpsychoactive one, cannabidiol, makes up about 40% of cannabis extracts, Dr. Breuner said. It’s been used as an anticonvulsant and to combat anxiety, psychosis, nausea and rheumatoid arthritis pain. In a study using a rat model for arthritis, inflammation and pain-related behaviors decreased in rats that received cannabidiol (Eur J Pain. 2016 Jul;20[6]:936-48).

A human dose would be about 160-300 mg daily, but side effects can include dry mouth, hypotension, lightheadedness, psychomotor slowing, sedation, and sleepiness.
 

Coenzyme Q10

This antioxidant is fat-soluble and has a chemical structure similar to vitamin K. It has been used in people with autism, chronic fatigue syndrome, fatigue from chemotherapy, Lyme disease, and muscular dystrophy, but the evidence focuses on fibromyalgia. One study of patients with fibromyalgia found that a 300-mg daily dose for 40 days reduced pain by 52%-56%, fatigue by 47%, morning tiredness by 56%, and tender points by 44%, compared with baseline (Antioxid Redox Signal. 2013;19[12]:1356-61.)

In another, 200 mg of coenzyme Q10 with 200 mg ginkgo daily for 3 months resulted in improvement of quality of life measures, including physical fitness levels, emotional feelings, social activities, overall health, and pain (J Int Med Res. 2002;30:195-9).

Potential adverse effects of coenzyme Q10 include nausea, vomiting, diarrhea, appetite suppression, and heartburn, albeit typically in less than 1% of patients.
 

Echinacea

magicflute002/Thinkstock

Echinacea actually is approved in Germany for supportive therapy in treating upper respiratory tract infections, urogenital infections, and wound healing, Dr. Breuner said. Hypothesized mechanisms of action include stimulation of the alternate complement pathway, immune-modulating effects, activating nonspecific T cells, inhibiting viral replication, and enhancing phagocytosis.

However, in clinical studies, echinacea did not reduce the duration or severity of upper respiratory tract infections or the occurrence or severity of infection, compared with placebo (JAMA. 2003 Dec 3;290[21]:2824-30; N Engl J Med. 2005 Jul 28;353[4]:341-8); this was tested in children aged 2-11 years in the first study, and the mean age of the subjects in the second study was 21 years. A 2014 Cochrane review found no overall benefits for treating common colds but noted the possibility of “a weak benefit from some echinacea products” based on individual trials with consistently positive, yet nonsignificant, trends, albeit with “questionable clinical relevance” (Cochrane Database Syst Rev. 2014 Feb 20;[2]:CD000530).

People with autoimmune conditions or who are immunocompromised should not use echinacea.
 

Magnesium

Magnesium also is used to treat migraines with a dose of 300-500 mg daily, although also it can be consumed in food, such as soy beans, black beans, tofu, seeds, nuts, whole grains, and shellfish (Expert Rev Neurother. 2009 Mar;9[3]:369-79; Neurology. 2012 Apr 24;78[17]:1346-53).

Side effects can include diarrhea and interactions with bisphosphonates, antibiotics] and diuretics. Taking proton pump inhibitors also may reduce magnesium levels.
 

Melatonin

Wjeger/Thinkstockphotos

Melatonin, a synthetic version of the hormone produced in humans to signal the onset of nighttime, has been studied extensively for jet lag, insomnia, shift-work disorder, circadian rhythm disorders, and withdrawal from benzodiazepine and nicotine.

Research shows that melatonin can improve sleep onset, duration, and quality. Some research has shown increased total sleep time (PLoS One. 2013 May 17;8(5):e63773).

Some evidence suggests it has endocrine-disrupting adverse effects, such as inhibiting ovulation and impairing glucose utilization.
 

N-acetyl cysteine (NAC)

Although it’s primarily an antidote for acetaminophen and carbon monoxide poisoning, NAC has been used for a wide range of conditions, including reducing lipoprotein levels with hyperlipidemia and reducing risk of cardiovascular events in people with end-stage renal disease and other conditions. It also has been used in people with bipolar disorder, schizophrenia, PTSD, substance disorders, and Tourette syndrome.

“Some clinical research shows that taking NAC 900 mg daily for 4 weeks, followed by 900 mg twice daily for 4 weeks and then 900 mg three times daily for 4 weeks improves symptoms of irritability in children with autism,” Dr. Breuner said. Other research showed reduced irritability in children with autism when they took 1,200 mg of NAC daily with risperidone, compared with risperidone alone. One study also has found “that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents” (Iran J Psychiatry. 2017 Apr;12[2]:134-141).

Side effects can include diarrhea, nausea, and heartburn.
 

Omega-3 fatty acids: DHA and EHA

Docosahexanoic acid (DHA) and eicosapentanoic acid (EHA) have been used to treat ADHD, depression, heart disease, and also to lower the risk of macular degeneration.

A systematic review of 25 randomized controlled trials of more than 3,600 subjects found that “omega-3 supplementation generally correlated with improvements in blood biomarkers” (Nutrients. 2018 Aug 15;10[8]. pii: E1094). A small study in children with Tourette syndrome found that omega-3 fatty acids did not reduce tic scores, but “may be beneficial in reduction of tic-related impairment” for some children and teens (Pediatrics. 2012 Jun;129[6]:e1493-500).

Possible adverse effects include fishy taste, belching, nosebleeds, nausea, loose stools, and – at higher doses – decreased blood coagulation.
 

St. John’s wort

Alexandru Magurean/Thinkstock

This herb has long been used to treat depression and appears to work by inhibiting serotonin reuptake, monoamine oxidase (MAO), 5-hydroxytryptamine (5-HT), dopamine, noradrenaline, gamma aminobutyric acid (GABA), and glutamate. A 2005 Cochrane review found St. John’s wort to work better than placebo with similar effectiveness as standard antidepressants for mild to moderate depression, but its benefit for major depression is questionable (Cochrane Database Syst Rev. 2005 Apr 18;[2]:CD000448).

An ideal dose is 300 mg daily, but physicians should be aware of the herb’s potential for certain drug interactions. It may increase metabolism of warfarin, cyclosporin, HIV protease inhibitors, theophylline, digoxin, and oral contraceptives (Expert Opin Drug Metab Toxicol. 2012 Jun;8[6]:691-708). Other potential side effects include decreased platelet aggregation, serotonin syndrome, and photosensitivity.
 

Turmeric (curcumin)

SyedMirazurRahman/Thinkstock

Turmeric is an anti-inflammatory agent used for a wide range of complaints, but research primarily has focused on its use for pain. No studies exist in children, but a handful of studies have found reduction in joint pain and rheumatoid arthritis symptoms in adults with 500-mg doses twice daily (Phytother Res. 2012 Nov;26[11]:1719-25; J Med Food. 2017 Oct;20[10]:1022-30). One of these studies focused on a specific product, Instaflex, that contained turmeric among multiple other active ingredients (Nutr J. 2013 Nov 25;12[1]:154).

Potential adverse effects of turmeric/curcumin include constipation, dyspepsia, diarrhea, dissension, reflux, nausea, vomiting, itching, and hives.
 

Zinc

ilkab/Thinkstock

Like echinacea, zinc is commonly used to treat the common cold. A 2013 Cochrane review of randomized, controlled trials found that taking zinc “within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people, but some caution is needed due to the heterogeneity of the data” (Cochrane Database Syst Rev. 2013 Jun 18;[6]:CD001364). The dose is 75 mg a day, and potential adverse effects include bad taste, nausea, and anosmia.

Dr. Breuner said she had no relevant financial disclosures.

NEW ORLEANS – With more than 10% of children receiving complementary or alternative medicine (CAM), you should be familiar with what does and doesn’t work when it comes to using supplements for various medical issues, said Cora Breuner, MD, a professor of pediatrics at the University of Washington, Seattle, and attending physician at Seattle Children’s Hospital.

Dr. Breuner presented an overview of more than a dozen popular supplements with their uses and evidence at the American Academy of Pediatrics annual meeting. Most of the evidence comes from studies in adults, not children, and the evidence overall is sometimes scant, but it can guide physicians in discussing options with parents interested in CAM.
 

Butterbur

This root primarily is used to treat migraines via anti-inflammatory effects. The ideal dose is 50-75 mg daily in 2-3 divided doses for children aged 8-9 years and 100-150 mg daily in 2-3 divided doses for those aged 10 and older (Headache. 2005 Mar;45:196-203; Eur J Pain. 2008;12:301-13; Neurology. 2012 Apr 24;78[17]:1346-53).

Adverse effects are mostly gastrointestinal, such as diarrhea and stomach upset, and dermal/allergic reactions, such as itchy eyes, asthma, and itching.
 

Caffeine

Caffeine is the most popular drug of choice for reducing drowsiness and increasing alertness and has the strongest evidence base, including for improving sports and work performance (J Strength Cond Res. 2010 Jan;24[1]:257-65). Regular caffeine use can lead to dependence, however, and it can cause anxiety, nervousness, irritability, insomnia, peptic ulcers, palpitations, gastroesophageal reflux disease (GERD), and tremors. Withdrawal can involve headaches, irritability, and anxiety.

Cannabidiol

Marijuana has more than 80 cannabinoids, and a nonpsychoactive one, cannabidiol, makes up about 40% of cannabis extracts, Dr. Breuner said. It’s been used as an anticonvulsant and to combat anxiety, psychosis, nausea and rheumatoid arthritis pain. In a study using a rat model for arthritis, inflammation and pain-related behaviors decreased in rats that received cannabidiol (Eur J Pain. 2016 Jul;20[6]:936-48).

A human dose would be about 160-300 mg daily, but side effects can include dry mouth, hypotension, lightheadedness, psychomotor slowing, sedation, and sleepiness.
 

Coenzyme Q10

This antioxidant is fat-soluble and has a chemical structure similar to vitamin K. It has been used in people with autism, chronic fatigue syndrome, fatigue from chemotherapy, Lyme disease, and muscular dystrophy, but the evidence focuses on fibromyalgia. One study of patients with fibromyalgia found that a 300-mg daily dose for 40 days reduced pain by 52%-56%, fatigue by 47%, morning tiredness by 56%, and tender points by 44%, compared with baseline (Antioxid Redox Signal. 2013;19[12]:1356-61.)

In another, 200 mg of coenzyme Q10 with 200 mg ginkgo daily for 3 months resulted in improvement of quality of life measures, including physical fitness levels, emotional feelings, social activities, overall health, and pain (J Int Med Res. 2002;30:195-9).

Potential adverse effects of coenzyme Q10 include nausea, vomiting, diarrhea, appetite suppression, and heartburn, albeit typically in less than 1% of patients.
 

Echinacea

magicflute002/Thinkstock

Echinacea actually is approved in Germany for supportive therapy in treating upper respiratory tract infections, urogenital infections, and wound healing, Dr. Breuner said. Hypothesized mechanisms of action include stimulation of the alternate complement pathway, immune-modulating effects, activating nonspecific T cells, inhibiting viral replication, and enhancing phagocytosis.

However, in clinical studies, echinacea did not reduce the duration or severity of upper respiratory tract infections or the occurrence or severity of infection, compared with placebo (JAMA. 2003 Dec 3;290[21]:2824-30; N Engl J Med. 2005 Jul 28;353[4]:341-8); this was tested in children aged 2-11 years in the first study, and the mean age of the subjects in the second study was 21 years. A 2014 Cochrane review found no overall benefits for treating common colds but noted the possibility of “a weak benefit from some echinacea products” based on individual trials with consistently positive, yet nonsignificant, trends, albeit with “questionable clinical relevance” (Cochrane Database Syst Rev. 2014 Feb 20;[2]:CD000530).

People with autoimmune conditions or who are immunocompromised should not use echinacea.
 

Magnesium

Magnesium also is used to treat migraines with a dose of 300-500 mg daily, although also it can be consumed in food, such as soy beans, black beans, tofu, seeds, nuts, whole grains, and shellfish (Expert Rev Neurother. 2009 Mar;9[3]:369-79; Neurology. 2012 Apr 24;78[17]:1346-53).

Side effects can include diarrhea and interactions with bisphosphonates, antibiotics] and diuretics. Taking proton pump inhibitors also may reduce magnesium levels.
 

Melatonin

Wjeger/Thinkstockphotos

Melatonin, a synthetic version of the hormone produced in humans to signal the onset of nighttime, has been studied extensively for jet lag, insomnia, shift-work disorder, circadian rhythm disorders, and withdrawal from benzodiazepine and nicotine.

Research shows that melatonin can improve sleep onset, duration, and quality. Some research has shown increased total sleep time (PLoS One. 2013 May 17;8(5):e63773).

Some evidence suggests it has endocrine-disrupting adverse effects, such as inhibiting ovulation and impairing glucose utilization.
 

N-acetyl cysteine (NAC)

Although it’s primarily an antidote for acetaminophen and carbon monoxide poisoning, NAC has been used for a wide range of conditions, including reducing lipoprotein levels with hyperlipidemia and reducing risk of cardiovascular events in people with end-stage renal disease and other conditions. It also has been used in people with bipolar disorder, schizophrenia, PTSD, substance disorders, and Tourette syndrome.

“Some clinical research shows that taking NAC 900 mg daily for 4 weeks, followed by 900 mg twice daily for 4 weeks and then 900 mg three times daily for 4 weeks improves symptoms of irritability in children with autism,” Dr. Breuner said. Other research showed reduced irritability in children with autism when they took 1,200 mg of NAC daily with risperidone, compared with risperidone alone. One study also has found “that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents” (Iran J Psychiatry. 2017 Apr;12[2]:134-141).

Side effects can include diarrhea, nausea, and heartburn.
 

Omega-3 fatty acids: DHA and EHA

Docosahexanoic acid (DHA) and eicosapentanoic acid (EHA) have been used to treat ADHD, depression, heart disease, and also to lower the risk of macular degeneration.

A systematic review of 25 randomized controlled trials of more than 3,600 subjects found that “omega-3 supplementation generally correlated with improvements in blood biomarkers” (Nutrients. 2018 Aug 15;10[8]. pii: E1094). A small study in children with Tourette syndrome found that omega-3 fatty acids did not reduce tic scores, but “may be beneficial in reduction of tic-related impairment” for some children and teens (Pediatrics. 2012 Jun;129[6]:e1493-500).

Possible adverse effects include fishy taste, belching, nosebleeds, nausea, loose stools, and – at higher doses – decreased blood coagulation.
 

St. John’s wort

Alexandru Magurean/Thinkstock

This herb has long been used to treat depression and appears to work by inhibiting serotonin reuptake, monoamine oxidase (MAO), 5-hydroxytryptamine (5-HT), dopamine, noradrenaline, gamma aminobutyric acid (GABA), and glutamate. A 2005 Cochrane review found St. John’s wort to work better than placebo with similar effectiveness as standard antidepressants for mild to moderate depression, but its benefit for major depression is questionable (Cochrane Database Syst Rev. 2005 Apr 18;[2]:CD000448).

An ideal dose is 300 mg daily, but physicians should be aware of the herb’s potential for certain drug interactions. It may increase metabolism of warfarin, cyclosporin, HIV protease inhibitors, theophylline, digoxin, and oral contraceptives (Expert Opin Drug Metab Toxicol. 2012 Jun;8[6]:691-708). Other potential side effects include decreased platelet aggregation, serotonin syndrome, and photosensitivity.
 

Turmeric (curcumin)

SyedMirazurRahman/Thinkstock

Turmeric is an anti-inflammatory agent used for a wide range of complaints, but research primarily has focused on its use for pain. No studies exist in children, but a handful of studies have found reduction in joint pain and rheumatoid arthritis symptoms in adults with 500-mg doses twice daily (Phytother Res. 2012 Nov;26[11]:1719-25; J Med Food. 2017 Oct;20[10]:1022-30). One of these studies focused on a specific product, Instaflex, that contained turmeric among multiple other active ingredients (Nutr J. 2013 Nov 25;12[1]:154).

Potential adverse effects of turmeric/curcumin include constipation, dyspepsia, diarrhea, dissension, reflux, nausea, vomiting, itching, and hives.
 

Zinc

ilkab/Thinkstock

Like echinacea, zinc is commonly used to treat the common cold. A 2013 Cochrane review of randomized, controlled trials found that taking zinc “within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people, but some caution is needed due to the heterogeneity of the data” (Cochrane Database Syst Rev. 2013 Jun 18;[6]:CD001364). The dose is 75 mg a day, and potential adverse effects include bad taste, nausea, and anosmia.

Dr. Breuner said she had no relevant financial disclosures.

NEW ORLEANS – More than 1 in 10 children (12%) have received complementary or alternative medicine (CAM), according to the 2012 National Health Interview Survey. It’s therefore vital that you are familiar with the options and evidence on these treatments, according to Cora Breuner, MD, a professor of pediatrics at the University of Washington, Seattle, and attending physician at Seattle Children’s Hospital.

“Use of CAM by a parent was strongly associated with the child’s use of CAM,” Dr. Breuner told attendees at the annual meeting of the American Academy of Pediatrics. Parents of children using CAM were more likely to have a college education and to use prescription medication, the National Health Interview Survey found, and teens were more frequent users of CAM than infants.

The most common conditions treated in children with CAM were back and neck pain, colds, anxiety, stress, ADHD, insomnia, and general musculoskeletal conditions or complaints. Fish oil, melatonin, probiotics, and chiropractic and osteopathic manipulation were used more frequently than any other CAM treatments, but Dr. Breuner’s presentation focused specifically on supplements, including vitamins and herbs.

Physicians generally know that regulation of supplements is far less strict than for prescription medication, but patients may be less aware of how lax the law is when it comes to the safety and effectiveness of vitamins, minerals, herbs, and other dietary supplements.

“Products can go on the market with no testing of efficacy, and companies do not have to prove that their products are safe – only offer reasonable assurance of safety,” Dr. Breuner explained. “Supplements do not have to be manufactured to any standards, and FDA [Food and Drug Administration] approval is not needed for package or marketing claims,” although the reputable manufacturers favor standards.

She cited a 2011 study of popular supplement products on the market that found 75% of them did not include key safety messages (BMC Med. 2011 Aug 9;9:94). The study focused on St. John’s wort, ginkgo, ginseng, garlic, and echinacea products, and it’s likely other products lack such safety information as well. Yet researchers have identified a wide range of potential adverse effects from herbal medicines (Clin Med [Lond]. 2013 Feb;13[1]:7-12).

Physicians and consumers can rely on a handful of voluntary standards and online databases to guide therapeutic decisions and learn more about the evidence on specific products. The U.S. Pharmacopeia Dietary Supplement Verification Program is a seal consumers can look for on supplement products that indicates the product meets stricter standards than what the FDA allows.

Other resources include ConsumerLab.com, the Natural Medicines Research Collaboration, and the Pubmed Dietary Supplement Subset database from the National Institute of Medicine. The latter contains more than 676,000 unique scientific citations on published studies about vitamins, minerals, and botanicals, Dr. Breuner said.

Dr. Breuner presented an overview of more than a dozen popular supplements that included their uses and the evidence related to their use. Although not exhaustive, her list included the most common supplements for which some research has been done: butterbur, caffeine, cannabidiol, coenzyme Q10, echinacea, magnesium, melatonin, N-acetylcysteine, omega 3 fatty acids, St. John’s wort, turmeric (curcumin), and zinc.

The findings from these studies, however, vary greatly, and the studies themselves are often small and limited to adults. Shared decision making is key in working with families interested in using CAM, and families should be aware that supplements can have side effects just as FDA-approved drugs do.

Dr. Breuner reported that she had no relevant financial disclosures.

NEW ORLEANS – More than 1 in 10 children (12%) have received complementary or alternative medicine (CAM), according to the 2012 National Health Interview Survey. It’s therefore vital that you are familiar with the options and evidence on these treatments, according to Cora Breuner, MD, a professor of pediatrics at the University of Washington, Seattle, and attending physician at Seattle Children’s Hospital.

“Use of CAM by a parent was strongly associated with the child’s use of CAM,” Dr. Breuner told attendees at the annual meeting of the American Academy of Pediatrics. Parents of children using CAM were more likely to have a college education and to use prescription medication, the National Health Interview Survey found, and teens were more frequent users of CAM than infants.

The most common conditions treated in children with CAM were back and neck pain, colds, anxiety, stress, ADHD, insomnia, and general musculoskeletal conditions or complaints. Fish oil, melatonin, probiotics, and chiropractic and osteopathic manipulation were used more frequently than any other CAM treatments, but Dr. Breuner’s presentation focused specifically on supplements, including vitamins and herbs.

Physicians generally know that regulation of supplements is far less strict than for prescription medication, but patients may be less aware of how lax the law is when it comes to the safety and effectiveness of vitamins, minerals, herbs, and other dietary supplements.

“Products can go on the market with no testing of efficacy, and companies do not have to prove that their products are safe – only offer reasonable assurance of safety,” Dr. Breuner explained. “Supplements do not have to be manufactured to any standards, and FDA [Food and Drug Administration] approval is not needed for package or marketing claims,” although the reputable manufacturers favor standards.

She cited a 2011 study of popular supplement products on the market that found 75% of them did not include key safety messages (BMC Med. 2011 Aug 9;9:94). The study focused on St. John’s wort, ginkgo, ginseng, garlic, and echinacea products, and it’s likely other products lack such safety information as well. Yet researchers have identified a wide range of potential adverse effects from herbal medicines (Clin Med [Lond]. 2013 Feb;13[1]:7-12).

Physicians and consumers can rely on a handful of voluntary standards and online databases to guide therapeutic decisions and learn more about the evidence on specific products. The U.S. Pharmacopeia Dietary Supplement Verification Program is a seal consumers can look for on supplement products that indicates the product meets stricter standards than what the FDA allows.

Other resources include ConsumerLab.com, the Natural Medicines Research Collaboration, and the Pubmed Dietary Supplement Subset database from the National Institute of Medicine. The latter contains more than 676,000 unique scientific citations on published studies about vitamins, minerals, and botanicals, Dr. Breuner said.

Dr. Breuner presented an overview of more than a dozen popular supplements that included their uses and the evidence related to their use. Although not exhaustive, her list included the most common supplements for which some research has been done: butterbur, caffeine, cannabidiol, coenzyme Q10, echinacea, magnesium, melatonin, N-acetylcysteine, omega 3 fatty acids, St. John’s wort, turmeric (curcumin), and zinc.

The findings from these studies, however, vary greatly, and the studies themselves are often small and limited to adults. Shared decision making is key in working with families interested in using CAM, and families should be aware that supplements can have side effects just as FDA-approved drugs do.

Dr. Breuner reported that she had no relevant financial disclosures.

NEW ORLEANS – More than 1 in 10 children (12%) have received complementary or alternative medicine (CAM), according to the 2012 National Health Interview Survey. It’s therefore vital that you are familiar with the options and evidence on these treatments, according to Cora Breuner, MD, a professor of pediatrics at the University of Washington, Seattle, and attending physician at Seattle Children’s Hospital.

“Use of CAM by a parent was strongly associated with the child’s use of CAM,” Dr. Breuner told attendees at the annual meeting of the American Academy of Pediatrics. Parents of children using CAM were more likely to have a college education and to use prescription medication, the National Health Interview Survey found, and teens were more frequent users of CAM than infants.

The most common conditions treated in children with CAM were back and neck pain, colds, anxiety, stress, ADHD, insomnia, and general musculoskeletal conditions or complaints. Fish oil, melatonin, probiotics, and chiropractic and osteopathic manipulation were used more frequently than any other CAM treatments, but Dr. Breuner’s presentation focused specifically on supplements, including vitamins and herbs.

Physicians generally know that regulation of supplements is far less strict than for prescription medication, but patients may be less aware of how lax the law is when it comes to the safety and effectiveness of vitamins, minerals, herbs, and other dietary supplements.

“Products can go on the market with no testing of efficacy, and companies do not have to prove that their products are safe – only offer reasonable assurance of safety,” Dr. Breuner explained. “Supplements do not have to be manufactured to any standards, and FDA [Food and Drug Administration] approval is not needed for package or marketing claims,” although the reputable manufacturers favor standards.

She cited a 2011 study of popular supplement products on the market that found 75% of them did not include key safety messages (BMC Med. 2011 Aug 9;9:94). The study focused on St. John’s wort, ginkgo, ginseng, garlic, and echinacea products, and it’s likely other products lack such safety information as well. Yet researchers have identified a wide range of potential adverse effects from herbal medicines (Clin Med [Lond]. 2013 Feb;13[1]:7-12).

Physicians and consumers can rely on a handful of voluntary standards and online databases to guide therapeutic decisions and learn more about the evidence on specific products. The U.S. Pharmacopeia Dietary Supplement Verification Program is a seal consumers can look for on supplement products that indicates the product meets stricter standards than what the FDA allows.

Other resources include ConsumerLab.com, the Natural Medicines Research Collaboration, and the Pubmed Dietary Supplement Subset database from the National Institute of Medicine. The latter contains more than 676,000 unique scientific citations on published studies about vitamins, minerals, and botanicals, Dr. Breuner said.

Dr. Breuner presented an overview of more than a dozen popular supplements that included their uses and the evidence related to their use. Although not exhaustive, her list included the most common supplements for which some research has been done: butterbur, caffeine, cannabidiol, coenzyme Q10, echinacea, magnesium, melatonin, N-acetylcysteine, omega 3 fatty acids, St. John’s wort, turmeric (curcumin), and zinc.

The findings from these studies, however, vary greatly, and the studies themselves are often small and limited to adults. Shared decision making is key in working with families interested in using CAM, and families should be aware that supplements can have side effects just as FDA-approved drugs do.

Dr. Breuner reported that she had no relevant financial disclosures.

The 2019 Novel Coronavirus (2019-nCoV) outbreak has unfolded so rapidly that many clinicians are scrambling to stay on top of it. Here are the answers to some frequently asked questions about how to prepare your clinic to respond to this outbreak.

Keep in mind that the outbreak is moving rapidly. Though scientific and epidemiologic knowledge has increased at unprecedented speed, there is much we don’t know, and some of what we think we know will change. Follow the links for the most up-to-date information.

What should our clinic do first?

Plan ahead with the following:

• Develop a plan for office staff to take travel histories from anyone with a respiratory illness and provide training for those who need it. Travel history at present should include asking about travel to China in the past 14 days, specifically Wuhan city or Hubei province.
• Review up-to-date infection control practices with all office staff and provide training for those who need it.
• Take an inventory of supplies of personal protective equipment (PPE), such as gowns, gloves, masks, eye protection, and N95 respirators or powered air-purifying respirators (PAPRs), and order items that are missing or low in stock.
• Fit-test users of N95 masks for maximal effectiveness.
• Plan where a potential patient would be isolated while obtaining expert advice.
• Know whom to contact at the state or local health department if you have a patient with the appropriate travel history.

The Centers for Disease Control and Prevention has prepared a toolkit to help frontline health care professionals prepare for this virus. Providers need to stay up to date on the latest recommendations, as the situation is changing rapidly.

When should I suspect 2019-nCoV illness, and what should I do?

Take the following steps to assess the concern and respond:

• If a patient with respiratory illness has traveled to China in the past 14 days, immediately put a mask on the patient and move the individual to a private room. Use a negative-pressure room if available.
• Put on appropriate PPE (including gloves, gown, eye protection, and mask) for contact, droplet, and airborne precautions. CDC recommends an N95 respirator mask if available, although we don’t know yet if there is true airborne spread.
• Obtain an accurate travel history, including dates and cities. (Tip: Get the correct spelling, as the English spelling of cities in China can cause confusion.)
• If the patient meets the current CDC definition of “person under investigation” or PUI, or if you need guidance on how to proceed, notify infection control (if you are in a facility that has it) and call your state or local health department immediately.
• Contact public health authorities who can help decide whether the patient should be admitted to airborne isolation or monitored at home with appropriate precautions.

What is the definition of a PUI?

The current definition of a PUI is a person who has fever and symptoms of a respiratory infection (cough, shortness of breath) AND who has EITHER been in Wuhan city or Hubei province in the past 14 days OR had close contact with a person either under investigation for 2019-nCoV infection or with confirmed infection. The definition of a PUI will change over time, so check this link.

How can I test for 2019-nCoV?

As of Jan. 30, 2020, testing is by polymerase chain reaction (PCR) and is available in the United States only through the CDC in Atlanta. Testing should soon be available in state health department laboratories. If public health authorities decide that your patient should be tested, they will instruct you on which samples to obtain.

The full sequence of 2019-nCoV has been shared, so some reference laboratories may develop and validate tests, ideally with assistance from CDC. If testing becomes available, make certain that it is a reputable lab that has carefully validated the test.

Should I test for other viruses?

Because the symptoms of 2019-nCoV infection overlap with those of influenza and other respiratory viruses, PCR testing for other viruses should be considered if it will change management (i.e., change the decision to provide influenza antivirals). Use appropriate PPE while collecting specimens, including eye protection. If 2019-nCoV is a consideration, you may want to send the specimen to a hospital lab for testing, where the sample will be processed under a biosafety hood, rather than doing point-of-care testing in the office.

How dangerous is 2019-nCoV?

The current estimated mortality rate is 2%-3%. That is probably an overestimate, as those with severe disease and those who die are more likely to be tested and reported early in an epidemic.

Our current knowledge is based on preliminary reports from hospitalized patients and will probably change. From the speed of spread and a single family cluster, it seems likely that there are milder cases and perhaps asymptomatic infection.

What else do I need to know about coronaviruses?

Coronaviruses are a large and diverse group of viruses, many of which are animal viruses. Before the discovery of the 2019-nCoV, six coronaviruses were known to infect humans. Four of these (HKU1, NL63, OC43, and 229E) predominantly caused mild to moderate upper respiratory illness, and they are thought to be responsible for 10%-30% of colds. They occasionally cause viral pneumonia and can be detected by some commercial multiplex panels.

Two other coronaviruses have caused outbreaks of severe respiratory illness in people: SARS, which emerged in Southern China in 2002, and MERS in the Middle East, in 2012. Unlike SARS, sporadic cases of MERS continue to occur.

The current outbreak is caused by 2019-nCoV, a previously unknown beta coronavirus. It is most closely related (~96%) to a bat virus and shares about 80% sequence homology with SARS CoV.

Andrew T. Pavia, MD, is the George and Esther Gross Presidential Professor and chief of the division of pediatric infectious disease in the department of pediatrics at the University of Utah, Salt Lake City. He is also director of hospital epidemiology and associate director of antimicrobial stewardship at Primary Children’s Hospital, Salt Lake City. Dr. Pavia has disclosed that he has served as a consultant for Genentech, Merck, and Seqirus and that he has served as associate editor for The Sanford Guide.

This article first appeared on Medscape.com.

The 2019 Novel Coronavirus (2019-nCoV) outbreak has unfolded so rapidly that many clinicians are scrambling to stay on top of it. Here are the answers to some frequently asked questions about how to prepare your clinic to respond to this outbreak.

Keep in mind that the outbreak is moving rapidly. Though scientific and epidemiologic knowledge has increased at unprecedented speed, there is much we don’t know, and some of what we think we know will change. Follow the links for the most up-to-date information.

What should our clinic do first?

Plan ahead with the following:

• Develop a plan for office staff to take travel histories from anyone with a respiratory illness and provide training for those who need it. Travel history at present should include asking about travel to China in the past 14 days, specifically Wuhan city or Hubei province.
• Review up-to-date infection control practices with all office staff and provide training for those who need it.
• Take an inventory of supplies of personal protective equipment (PPE), such as gowns, gloves, masks, eye protection, and N95 respirators or powered air-purifying respirators (PAPRs), and order items that are missing or low in stock.
• Fit-test users of N95 masks for maximal effectiveness.
• Plan where a potential patient would be isolated while obtaining expert advice.
• Know whom to contact at the state or local health department if you have a patient with the appropriate travel history.

The Centers for Disease Control and Prevention has prepared a toolkit to help frontline health care professionals prepare for this virus. Providers need to stay up to date on the latest recommendations, as the situation is changing rapidly.

When should I suspect 2019-nCoV illness, and what should I do?

Take the following steps to assess the concern and respond:

• If a patient with respiratory illness has traveled to China in the past 14 days, immediately put a mask on the patient and move the individual to a private room. Use a negative-pressure room if available.
• Put on appropriate PPE (including gloves, gown, eye protection, and mask) for contact, droplet, and airborne precautions. CDC recommends an N95 respirator mask if available, although we don’t know yet if there is true airborne spread.
• Obtain an accurate travel history, including dates and cities. (Tip: Get the correct spelling, as the English spelling of cities in China can cause confusion.)
• If the patient meets the current CDC definition of “person under investigation” or PUI, or if you need guidance on how to proceed, notify infection control (if you are in a facility that has it) and call your state or local health department immediately.
• Contact public health authorities who can help decide whether the patient should be admitted to airborne isolation or monitored at home with appropriate precautions.

What is the definition of a PUI?

The current definition of a PUI is a person who has fever and symptoms of a respiratory infection (cough, shortness of breath) AND who has EITHER been in Wuhan city or Hubei province in the past 14 days OR had close contact with a person either under investigation for 2019-nCoV infection or with confirmed infection. The definition of a PUI will change over time, so check this link.

How can I test for 2019-nCoV?

As of Jan. 30, 2020, testing is by polymerase chain reaction (PCR) and is available in the United States only through the CDC in Atlanta. Testing should soon be available in state health department laboratories. If public health authorities decide that your patient should be tested, they will instruct you on which samples to obtain.

The full sequence of 2019-nCoV has been shared, so some reference laboratories may develop and validate tests, ideally with assistance from CDC. If testing becomes available, make certain that it is a reputable lab that has carefully validated the test.

Should I test for other viruses?

Because the symptoms of 2019-nCoV infection overlap with those of influenza and other respiratory viruses, PCR testing for other viruses should be considered if it will change management (i.e., change the decision to provide influenza antivirals). Use appropriate PPE while collecting specimens, including eye protection. If 2019-nCoV is a consideration, you may want to send the specimen to a hospital lab for testing, where the sample will be processed under a biosafety hood, rather than doing point-of-care testing in the office.

How dangerous is 2019-nCoV?

The current estimated mortality rate is 2%-3%. That is probably an overestimate, as those with severe disease and those who die are more likely to be tested and reported early in an epidemic.

Our current knowledge is based on preliminary reports from hospitalized patients and will probably change. From the speed of spread and a single family cluster, it seems likely that there are milder cases and perhaps asymptomatic infection.

What else do I need to know about coronaviruses?

Coronaviruses are a large and diverse group of viruses, many of which are animal viruses. Before the discovery of the 2019-nCoV, six coronaviruses were known to infect humans. Four of these (HKU1, NL63, OC43, and 229E) predominantly caused mild to moderate upper respiratory illness, and they are thought to be responsible for 10%-30% of colds. They occasionally cause viral pneumonia and can be detected by some commercial multiplex panels.

Two other coronaviruses have caused outbreaks of severe respiratory illness in people: SARS, which emerged in Southern China in 2002, and MERS in the Middle East, in 2012. Unlike SARS, sporadic cases of MERS continue to occur.

The current outbreak is caused by 2019-nCoV, a previously unknown beta coronavirus. It is most closely related (~96%) to a bat virus and shares about 80% sequence homology with SARS CoV.

Andrew T. Pavia, MD, is the George and Esther Gross Presidential Professor and chief of the division of pediatric infectious disease in the department of pediatrics at the University of Utah, Salt Lake City. He is also director of hospital epidemiology and associate director of antimicrobial stewardship at Primary Children’s Hospital, Salt Lake City. Dr. Pavia has disclosed that he has served as a consultant for Genentech, Merck, and Seqirus and that he has served as associate editor for The Sanford Guide.

This article first appeared on Medscape.com.

The 2019 Novel Coronavirus (2019-nCoV) outbreak has unfolded so rapidly that many clinicians are scrambling to stay on top of it. Here are the answers to some frequently asked questions about how to prepare your clinic to respond to this outbreak.

Keep in mind that the outbreak is moving rapidly. Though scientific and epidemiologic knowledge has increased at unprecedented speed, there is much we don’t know, and some of what we think we know will change. Follow the links for the most up-to-date information.

What should our clinic do first?

Plan ahead with the following:

• Develop a plan for office staff to take travel histories from anyone with a respiratory illness and provide training for those who need it. Travel history at present should include asking about travel to China in the past 14 days, specifically Wuhan city or Hubei province.
• Review up-to-date infection control practices with all office staff and provide training for those who need it.
• Take an inventory of supplies of personal protective equipment (PPE), such as gowns, gloves, masks, eye protection, and N95 respirators or powered air-purifying respirators (PAPRs), and order items that are missing or low in stock.
• Fit-test users of N95 masks for maximal effectiveness.
• Plan where a potential patient would be isolated while obtaining expert advice.
• Know whom to contact at the state or local health department if you have a patient with the appropriate travel history.

The Centers for Disease Control and Prevention has prepared a toolkit to help frontline health care professionals prepare for this virus. Providers need to stay up to date on the latest recommendations, as the situation is changing rapidly.

When should I suspect 2019-nCoV illness, and what should I do?

Take the following steps to assess the concern and respond:

• If a patient with respiratory illness has traveled to China in the past 14 days, immediately put a mask on the patient and move the individual to a private room. Use a negative-pressure room if available.
• Put on appropriate PPE (including gloves, gown, eye protection, and mask) for contact, droplet, and airborne precautions. CDC recommends an N95 respirator mask if available, although we don’t know yet if there is true airborne spread.
• Obtain an accurate travel history, including dates and cities. (Tip: Get the correct spelling, as the English spelling of cities in China can cause confusion.)
• If the patient meets the current CDC definition of “person under investigation” or PUI, or if you need guidance on how to proceed, notify infection control (if you are in a facility that has it) and call your state or local health department immediately.
• Contact public health authorities who can help decide whether the patient should be admitted to airborne isolation or monitored at home with appropriate precautions.

What is the definition of a PUI?

The current definition of a PUI is a person who has fever and symptoms of a respiratory infection (cough, shortness of breath) AND who has EITHER been in Wuhan city or Hubei province in the past 14 days OR had close contact with a person either under investigation for 2019-nCoV infection or with confirmed infection. The definition of a PUI will change over time, so check this link.

How can I test for 2019-nCoV?

As of Jan. 30, 2020, testing is by polymerase chain reaction (PCR) and is available in the United States only through the CDC in Atlanta. Testing should soon be available in state health department laboratories. If public health authorities decide that your patient should be tested, they will instruct you on which samples to obtain.

The full sequence of 2019-nCoV has been shared, so some reference laboratories may develop and validate tests, ideally with assistance from CDC. If testing becomes available, make certain that it is a reputable lab that has carefully validated the test.

Should I test for other viruses?

Because the symptoms of 2019-nCoV infection overlap with those of influenza and other respiratory viruses, PCR testing for other viruses should be considered if it will change management (i.e., change the decision to provide influenza antivirals). Use appropriate PPE while collecting specimens, including eye protection. If 2019-nCoV is a consideration, you may want to send the specimen to a hospital lab for testing, where the sample will be processed under a biosafety hood, rather than doing point-of-care testing in the office.

How dangerous is 2019-nCoV?

The current estimated mortality rate is 2%-3%. That is probably an overestimate, as those with severe disease and those who die are more likely to be tested and reported early in an epidemic.

Our current knowledge is based on preliminary reports from hospitalized patients and will probably change. From the speed of spread and a single family cluster, it seems likely that there are milder cases and perhaps asymptomatic infection.

What else do I need to know about coronaviruses?

Coronaviruses are a large and diverse group of viruses, many of which are animal viruses. Before the discovery of the 2019-nCoV, six coronaviruses were known to infect humans. Four of these (HKU1, NL63, OC43, and 229E) predominantly caused mild to moderate upper respiratory illness, and they are thought to be responsible for 10%-30% of colds. They occasionally cause viral pneumonia and can be detected by some commercial multiplex panels.

Two other coronaviruses have caused outbreaks of severe respiratory illness in people: SARS, which emerged in Southern China in 2002, and MERS in the Middle East, in 2012. Unlike SARS, sporadic cases of MERS continue to occur.

The current outbreak is caused by 2019-nCoV, a previously unknown beta coronavirus. It is most closely related (~96%) to a bat virus and shares about 80% sequence homology with SARS CoV.

Andrew T. Pavia, MD, is the George and Esther Gross Presidential Professor and chief of the division of pediatric infectious disease in the department of pediatrics at the University of Utah, Salt Lake City. He is also director of hospital epidemiology and associate director of antimicrobial stewardship at Primary Children’s Hospital, Salt Lake City. Dr. Pavia has disclosed that he has served as a consultant for Genentech, Merck, and Seqirus and that he has served as associate editor for The Sanford Guide.

This article first appeared on Medscape.com.

England’s ban on smoking in cars carrying children led to a 72% relative reduction in the percentage of children self-reporting exposure to tobacco smoke in cars.

“Given children’s known vulnerability to secondhand smoke, reductions in exposure will probably result in improved health,” wrote Anthony A. Laverty, PhD, of Imperial College London and coauthors. Their findings were published in Thorax.

To determine the impact of a 2015 ban on smoking in cars carrying children in England and a 2016 ban in Scotland, the researchers analyzed survey data from 2012, 2014, and 2016 for each of the two countries. In England, children aged 13-15 years were asked, “In the past year, how often were you in a car with somebody smoking?” In Scotland, they were asked, “Are you regularly exposed to other people’s tobacco smoke in any of these places?” with cars/vehicles being one of the options.

Overall, 15,318 responses were received in England and 822 were received in Scotland. In England, self-reported regular exposure to smoke in cars was 6% in 2012, 6% in 2014 and 2% in 2016. In Scotland, it was 3% in 2012, 2% in 2014 and 1% in 2016. From 2014-2016 in England, implementation of the smoke-free policy was associated with a 4% absolute reduction – or a 72% relative reduction – in the percentage of children self-reporting exposure.

The authors acknowledged their study’s limitations, including exposure being based on self-reporting alone and the analyses using only three data points. “Future analyses with more data are recommended,” they wrote, “and may provide discrepant results.”

The study was funded by the National Institute for Health Research School for Public Health Research. One author was funded by the Medical Research Council on a clinician scientist fellowship. The others reported no potential conflicts of interest.

SOURCE: Laverty AA et al. Thorax. 2020 Jan 27. doi: 10.1136/thoraxjnl-2019-213998.

England’s ban on smoking in cars carrying children led to a 72% relative reduction in the percentage of children self-reporting exposure to tobacco smoke in cars.

“Given children’s known vulnerability to secondhand smoke, reductions in exposure will probably result in improved health,” wrote Anthony A. Laverty, PhD, of Imperial College London and coauthors. Their findings were published in Thorax.

To determine the impact of a 2015 ban on smoking in cars carrying children in England and a 2016 ban in Scotland, the researchers analyzed survey data from 2012, 2014, and 2016 for each of the two countries. In England, children aged 13-15 years were asked, “In the past year, how often were you in a car with somebody smoking?” In Scotland, they were asked, “Are you regularly exposed to other people’s tobacco smoke in any of these places?” with cars/vehicles being one of the options.

Overall, 15,318 responses were received in England and 822 were received in Scotland. In England, self-reported regular exposure to smoke in cars was 6% in 2012, 6% in 2014 and 2% in 2016. In Scotland, it was 3% in 2012, 2% in 2014 and 1% in 2016. From 2014-2016 in England, implementation of the smoke-free policy was associated with a 4% absolute reduction – or a 72% relative reduction – in the percentage of children self-reporting exposure.

The authors acknowledged their study’s limitations, including exposure being based on self-reporting alone and the analyses using only three data points. “Future analyses with more data are recommended,” they wrote, “and may provide discrepant results.”

The study was funded by the National Institute for Health Research School for Public Health Research. One author was funded by the Medical Research Council on a clinician scientist fellowship. The others reported no potential conflicts of interest.

SOURCE: Laverty AA et al. Thorax. 2020 Jan 27. doi: 10.1136/thoraxjnl-2019-213998.

England’s ban on smoking in cars carrying children led to a 72% relative reduction in the percentage of children self-reporting exposure to tobacco smoke in cars.

“Given children’s known vulnerability to secondhand smoke, reductions in exposure will probably result in improved health,” wrote Anthony A. Laverty, PhD, of Imperial College London and coauthors. Their findings were published in Thorax.

To determine the impact of a 2015 ban on smoking in cars carrying children in England and a 2016 ban in Scotland, the researchers analyzed survey data from 2012, 2014, and 2016 for each of the two countries. In England, children aged 13-15 years were asked, “In the past year, how often were you in a car with somebody smoking?” In Scotland, they were asked, “Are you regularly exposed to other people’s tobacco smoke in any of these places?” with cars/vehicles being one of the options.

Overall, 15,318 responses were received in England and 822 were received in Scotland. In England, self-reported regular exposure to smoke in cars was 6% in 2012, 6% in 2014 and 2% in 2016. In Scotland, it was 3% in 2012, 2% in 2014 and 1% in 2016. From 2014-2016 in England, implementation of the smoke-free policy was associated with a 4% absolute reduction – or a 72% relative reduction – in the percentage of children self-reporting exposure.

The authors acknowledged their study’s limitations, including exposure being based on self-reporting alone and the analyses using only three data points. “Future analyses with more data are recommended,” they wrote, “and may provide discrepant results.”

The study was funded by the National Institute for Health Research School for Public Health Research. One author was funded by the Medical Research Council on a clinician scientist fellowship. The others reported no potential conflicts of interest.

SOURCE: Laverty AA et al. Thorax. 2020 Jan 27. doi: 10.1136/thoraxjnl-2019-213998.

Although biosimilar versions of tumor necrosis factor inhibitors (TNFis) have been available to U.S. rheumatologists and their patients for over 3 years, uptake has thus far been slow.

monkeybusinessimages/thinkstockphotos.com

In an analysis of data from a large commercial payer, the two available biosimilars for infliximab (Remicade) accounted for less than 1% of TNFi prescribing since the first biosimilar to infliximab was approved in 2016.

The study, published in Arthritis & Rheumatology, involved a total of 1.1 million TNFi prescriptions or infusions received by 95,906 patients from 2016 to 2019. Investigators found that uptake of biosimilar infliximab was essentially flat, standing at 0.1% of prescribing in the second quarter of 2017, and topping out at 0.9% in the first quarter of 2019. For branded infliximab, prescribing was also stable, but accounted for about 20% of overall biologic dispensing in each quarter of the period studied.

There are currently two biosimilar medications to the originator infliximab, which is one of five originator biologics available to treat rheumatic diseases in the United States: infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). The former was approved in 2016 and the latter in 2017, said study author Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her coauthors.

“Our paper reports a disappointingly low uptake of biosimilar infliximab since the first quarter of 2017 using claims data from a large private health plan. The main and maybe the only reason to consider using a biosimilar is cost saving,” said Dr. Kim in an interview. “Our results suggest that current modest cost savings from infliximab biosimilars in the U.S. are not sufficient to promote their widespread use.”

In the payer database study conducted by Dr. Kim and colleagues, the insurer paid similar mean amounts per patient per quarter for originator and biosimilar infliximab in mid-2017 ($8,322 versus $8,656). By the end of 2018, a gap appeared, with the insurer paying a mean quarterly per-patient sum of $8,111 for biosimilar infliximab compared with $9,535 for the branded biologic.

“The lack of market penetration and very modest price reductions for biosimilars have left policymakers, payers, physicians, and the public frustrated, particularly because sales in Europe continue to rapidly expand and robust cost-savings have materialized,” wrote Jinoos Yazdany, MD, MPH, in an editorial accompanying the study.

Dr. Yazdany, professor and chief of the division of rheumatology at the University of California, San Francisco, noted that increased spending on biologics in the United States – which increased by 50% from 2014 to 2018 – has been driven by rising prices as well as increased uptake of biologic therapies.

At least in part, Europe has been able to reap cost savings where the United States hasn’t because fundamental differences in health care reimbursement can ease sweeping biosimilar adoption, Dr. Yazdany noted. “Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems have instituted a winner-takes-all bidding system,” with Denmark seeing cost savings of up to two-thirds when bidding was combined with mandatory switching, she said.

The continued market dominance of originator infliximab means that savings from biosimilars have thus far amounted to about $91 million, far short of the $1 billion that the Congressional Budget Office had projected for this date, Dr. Yazdany said.

One problem in the adoption of biosimilars by U.S. rheumatologists may have been uneven marketing and pricing across different types of practice, Colin C. Edgerton, MD, a rheumatologist at Low Country Rheumatology in South Carolina and chair of the American College of Rheumatology’s Committee on Rheumatologic Care, said in an interview.

“Rheumatologists have generally developed comfort with biosimilars, although this is not universal. The core message, that all biologics vary and that this is OK, is getting out. In general, rheumatologists also understand the problem with high drug prices and the threat to patient access,” Dr. Edgerton said. But “the early marketing and pricing focus for biosimilars seemed to be on hospitals and facilities, and this did not work effectively for community rheumatologists, where the majority of care is delivered. We have been pleased to see a manufacturer pivot toward community rheumatology where additional efforts need to be made to bend the curve on biosimilar adoption. It is critical for practices with experience using biosimilars to educate peers, and this is where networks of practicing rheumatologists are important.”

In Dr. Yazdany’s editorial, she cited four structural factors impeding biosimilar uptake and downstream savings.

First, she cites ongoing actions by pharmaceutical companies, which create a “patent thicket” that has the effect of fencing off originator biologics from biosimilars long beyond the original 12-year exclusivity period. Supporting the notion that “patent thickets” are a common strategy, Dr. Yazdany noted that almost half of the patent applications that AbbVie has filed for adalimumab (Humira) have come in after the original exclusivity period expired in 2014. Humira’s price has risen 18% yearly during this period.

The complicated role played by pharmacy benefit managers (PBMs) is another factor in slow adoption, said Dr. Yazdany: When manufacturers offer rebates to PBMs, the price of the originator biologic may be less than its biosimilar. Further, manufacturers may sign multiyear rebate agreements just before a biosimilar launch; PBMs are also sometimes threatened with the withdrawal of rebates if they offer biosimilars, she noted.

Third, prescriber inertia may also be at play, Dr. Yazdany noted, not least because patients often see little difference in out-of-pocket costs when they make the switch to a biosimilar – PBM rebates are not necessarily passed on to patients. Payers may not reimburse a biosimilar, or formularies can be built without them, influencing prescribing, and there’s usually no reimbursement incentive for biosimilar prescribing in the nonpublic sector, she said. To the contrary, infusing a drug with a higher price often means higher reimbursement for the administering clinician, since commercial insurance reimbursement is often calculated as a percent of the charge for the drug.

Further contributing to inertia is the extra time required for patient education and writing a new set of orders – all work that can’t be captured for extra reimbursement. Dr. Edgerton said that rheumatologists can talk with patients about the “nocebo effect” relating to biosimilars. “This is a phenomenon in which patients are thought to experience worsening symptoms associated with negative beliefs about biosimilars. There has been a study in Arthritis Care & Research addressing this concern. The authors found that positive framing of biosimilars led to more participants being willing to switch than negative framing. This suggests that clinicians have an important role in informing patients about biosimilars, and addressing hesitancy.”

Finally, Dr. Yazdany pointed out that for a pharmaceutical company pursuing biosimilar approval, the regulatory pathway itself can provide its own set of complications and confusion. Biosimilars are not exact molecular replicas of the originator biologic, and these differences can change efficacy and immunogenicity, and also affect stability. Hence, a company wishing to market a biosimilar has to show the Food and Drug Administration that safety and efficacy aren’t affected by a switch to biosimilar from an originator biologic. Extrapolation from one indication to another can be made – with scientific justification.

Rheumatologists are mindful of the potential differences between biosimilars and the originator biologic, as evinced in a recent position statement from the American College of Rheumatology. The position statement advises that “extrapolation should be pursued with caution,” and asks for clear labeling when biosimilars have been designated “interchangeable” with their biosimilar. Interchangeability can clear the way for pharmacy substitution of a prescribed biologic, though Dr. Yazdany noted that 40 states have passed legislation requiring prescriber notification.

The FDA is currently using postmarketing pharmacovigilance to monitor biosimilar performance in the real world, and a recent systematic review “should provide some reassurance,” wrote Dr. Yazdany, citing the study, which looked at 14,000 patients who had a total of 14 disease indications for biosimilar use. The 90-article review largely found no differences in safety, efficacy, or immunogenicity between originators and their biosimilars. Dr. Yazdany recommended greater openness to incorporating the European experience in the FDA’s ongoing reassessment.

A further way forward can come through tackling the patent thicket with the proposed bipartisan Biologic Patent Transparency Act, which would require publication of biologic patents in a one-stop publicly searchable database. Going further with legislation to address anticompetitive activity by pharmaceutical companies could shorten the runway to biosimilar launching considerably, she noted.

The complicated landscape of PBMs and rebates affects many sectors of health care, and new policy efforts are needed here as well, she said. Reimbursement strategies – and much-needed continuing medical education – can both ease prescriber unfamiliarity with biosimilars and provide incentives for their use, she concluded.

Dr. Kim concurred that change is needed before the United States is likely to reap significant economic benefit from biosimilars. “The uptake of biosimilars and their impact on overall health care cost needs to be reevaluated when we have more biosimilars available in the next 3-4 years. However, for now, it appears that substantial savings achieved in some European countries – for example, Denmark – may not be possible without systemic reform of the U.S. pharmaceutical market,” she said.

Dr. Yazdany is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and the National Institutes of Health. She has received independent research grants from Pfizer and Genentech and research consulting fees from Eli Lilly and AstraZeneca.

Dr. Kim’s study was supported by the division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Arnold Ventures. Dr. Kim has received research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche.

[email protected]

SOURCES: Kim SC et al. Arthritis Rheumatol. 2020 Jan 13. doi: 10.1002/art.41201; Yazdany J. Arthritis Rheumatol. 2020 Jan 10. doi: 10.1002/art.41203.

Although biosimilar versions of tumor necrosis factor inhibitors (TNFis) have been available to U.S. rheumatologists and their patients for over 3 years, uptake has thus far been slow.

monkeybusinessimages/thinkstockphotos.com

In an analysis of data from a large commercial payer, the two available biosimilars for infliximab (Remicade) accounted for less than 1% of TNFi prescribing since the first biosimilar to infliximab was approved in 2016.

The study, published in Arthritis & Rheumatology, involved a total of 1.1 million TNFi prescriptions or infusions received by 95,906 patients from 2016 to 2019. Investigators found that uptake of biosimilar infliximab was essentially flat, standing at 0.1% of prescribing in the second quarter of 2017, and topping out at 0.9% in the first quarter of 2019. For branded infliximab, prescribing was also stable, but accounted for about 20% of overall biologic dispensing in each quarter of the period studied.

There are currently two biosimilar medications to the originator infliximab, which is one of five originator biologics available to treat rheumatic diseases in the United States: infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). The former was approved in 2016 and the latter in 2017, said study author Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her coauthors.

“Our paper reports a disappointingly low uptake of biosimilar infliximab since the first quarter of 2017 using claims data from a large private health plan. The main and maybe the only reason to consider using a biosimilar is cost saving,” said Dr. Kim in an interview. “Our results suggest that current modest cost savings from infliximab biosimilars in the U.S. are not sufficient to promote their widespread use.”

In the payer database study conducted by Dr. Kim and colleagues, the insurer paid similar mean amounts per patient per quarter for originator and biosimilar infliximab in mid-2017 ($8,322 versus $8,656). By the end of 2018, a gap appeared, with the insurer paying a mean quarterly per-patient sum of $8,111 for biosimilar infliximab compared with $9,535 for the branded biologic.

“The lack of market penetration and very modest price reductions for biosimilars have left policymakers, payers, physicians, and the public frustrated, particularly because sales in Europe continue to rapidly expand and robust cost-savings have materialized,” wrote Jinoos Yazdany, MD, MPH, in an editorial accompanying the study.

Dr. Yazdany, professor and chief of the division of rheumatology at the University of California, San Francisco, noted that increased spending on biologics in the United States – which increased by 50% from 2014 to 2018 – has been driven by rising prices as well as increased uptake of biologic therapies.

At least in part, Europe has been able to reap cost savings where the United States hasn’t because fundamental differences in health care reimbursement can ease sweeping biosimilar adoption, Dr. Yazdany noted. “Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems have instituted a winner-takes-all bidding system,” with Denmark seeing cost savings of up to two-thirds when bidding was combined with mandatory switching, she said.

The continued market dominance of originator infliximab means that savings from biosimilars have thus far amounted to about $91 million, far short of the $1 billion that the Congressional Budget Office had projected for this date, Dr. Yazdany said.

One problem in the adoption of biosimilars by U.S. rheumatologists may have been uneven marketing and pricing across different types of practice, Colin C. Edgerton, MD, a rheumatologist at Low Country Rheumatology in South Carolina and chair of the American College of Rheumatology’s Committee on Rheumatologic Care, said in an interview.

“Rheumatologists have generally developed comfort with biosimilars, although this is not universal. The core message, that all biologics vary and that this is OK, is getting out. In general, rheumatologists also understand the problem with high drug prices and the threat to patient access,” Dr. Edgerton said. But “the early marketing and pricing focus for biosimilars seemed to be on hospitals and facilities, and this did not work effectively for community rheumatologists, where the majority of care is delivered. We have been pleased to see a manufacturer pivot toward community rheumatology where additional efforts need to be made to bend the curve on biosimilar adoption. It is critical for practices with experience using biosimilars to educate peers, and this is where networks of practicing rheumatologists are important.”

In Dr. Yazdany’s editorial, she cited four structural factors impeding biosimilar uptake and downstream savings.

First, she cites ongoing actions by pharmaceutical companies, which create a “patent thicket” that has the effect of fencing off originator biologics from biosimilars long beyond the original 12-year exclusivity period. Supporting the notion that “patent thickets” are a common strategy, Dr. Yazdany noted that almost half of the patent applications that AbbVie has filed for adalimumab (Humira) have come in after the original exclusivity period expired in 2014. Humira’s price has risen 18% yearly during this period.

The complicated role played by pharmacy benefit managers (PBMs) is another factor in slow adoption, said Dr. Yazdany: When manufacturers offer rebates to PBMs, the price of the originator biologic may be less than its biosimilar. Further, manufacturers may sign multiyear rebate agreements just before a biosimilar launch; PBMs are also sometimes threatened with the withdrawal of rebates if they offer biosimilars, she noted.

Third, prescriber inertia may also be at play, Dr. Yazdany noted, not least because patients often see little difference in out-of-pocket costs when they make the switch to a biosimilar – PBM rebates are not necessarily passed on to patients. Payers may not reimburse a biosimilar, or formularies can be built without them, influencing prescribing, and there’s usually no reimbursement incentive for biosimilar prescribing in the nonpublic sector, she said. To the contrary, infusing a drug with a higher price often means higher reimbursement for the administering clinician, since commercial insurance reimbursement is often calculated as a percent of the charge for the drug.

Further contributing to inertia is the extra time required for patient education and writing a new set of orders – all work that can’t be captured for extra reimbursement. Dr. Edgerton said that rheumatologists can talk with patients about the “nocebo effect” relating to biosimilars. “This is a phenomenon in which patients are thought to experience worsening symptoms associated with negative beliefs about biosimilars. There has been a study in Arthritis Care & Research addressing this concern. The authors found that positive framing of biosimilars led to more participants being willing to switch than negative framing. This suggests that clinicians have an important role in informing patients about biosimilars, and addressing hesitancy.”

Finally, Dr. Yazdany pointed out that for a pharmaceutical company pursuing biosimilar approval, the regulatory pathway itself can provide its own set of complications and confusion. Biosimilars are not exact molecular replicas of the originator biologic, and these differences can change efficacy and immunogenicity, and also affect stability. Hence, a company wishing to market a biosimilar has to show the Food and Drug Administration that safety and efficacy aren’t affected by a switch to biosimilar from an originator biologic. Extrapolation from one indication to another can be made – with scientific justification.

Rheumatologists are mindful of the potential differences between biosimilars and the originator biologic, as evinced in a recent position statement from the American College of Rheumatology. The position statement advises that “extrapolation should be pursued with caution,” and asks for clear labeling when biosimilars have been designated “interchangeable” with their biosimilar. Interchangeability can clear the way for pharmacy substitution of a prescribed biologic, though Dr. Yazdany noted that 40 states have passed legislation requiring prescriber notification.

The FDA is currently using postmarketing pharmacovigilance to monitor biosimilar performance in the real world, and a recent systematic review “should provide some reassurance,” wrote Dr. Yazdany, citing the study, which looked at 14,000 patients who had a total of 14 disease indications for biosimilar use. The 90-article review largely found no differences in safety, efficacy, or immunogenicity between originators and their biosimilars. Dr. Yazdany recommended greater openness to incorporating the European experience in the FDA’s ongoing reassessment.

A further way forward can come through tackling the patent thicket with the proposed bipartisan Biologic Patent Transparency Act, which would require publication of biologic patents in a one-stop publicly searchable database. Going further with legislation to address anticompetitive activity by pharmaceutical companies could shorten the runway to biosimilar launching considerably, she noted.

The complicated landscape of PBMs and rebates affects many sectors of health care, and new policy efforts are needed here as well, she said. Reimbursement strategies – and much-needed continuing medical education – can both ease prescriber unfamiliarity with biosimilars and provide incentives for their use, she concluded.

Dr. Kim concurred that change is needed before the United States is likely to reap significant economic benefit from biosimilars. “The uptake of biosimilars and their impact on overall health care cost needs to be reevaluated when we have more biosimilars available in the next 3-4 years. However, for now, it appears that substantial savings achieved in some European countries – for example, Denmark – may not be possible without systemic reform of the U.S. pharmaceutical market,” she said.

Dr. Yazdany is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and the National Institutes of Health. She has received independent research grants from Pfizer and Genentech and research consulting fees from Eli Lilly and AstraZeneca.

Dr. Kim’s study was supported by the division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Arnold Ventures. Dr. Kim has received research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche.

[email protected]

SOURCES: Kim SC et al. Arthritis Rheumatol. 2020 Jan 13. doi: 10.1002/art.41201; Yazdany J. Arthritis Rheumatol. 2020 Jan 10. doi: 10.1002/art.41203.

Although biosimilar versions of tumor necrosis factor inhibitors (TNFis) have been available to U.S. rheumatologists and their patients for over 3 years, uptake has thus far been slow.

monkeybusinessimages/thinkstockphotos.com

In an analysis of data from a large commercial payer, the two available biosimilars for infliximab (Remicade) accounted for less than 1% of TNFi prescribing since the first biosimilar to infliximab was approved in 2016.

The study, published in Arthritis & Rheumatology, involved a total of 1.1 million TNFi prescriptions or infusions received by 95,906 patients from 2016 to 2019. Investigators found that uptake of biosimilar infliximab was essentially flat, standing at 0.1% of prescribing in the second quarter of 2017, and topping out at 0.9% in the first quarter of 2019. For branded infliximab, prescribing was also stable, but accounted for about 20% of overall biologic dispensing in each quarter of the period studied.

There are currently two biosimilar medications to the originator infliximab, which is one of five originator biologics available to treat rheumatic diseases in the United States: infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). The former was approved in 2016 and the latter in 2017, said study author Seoyoung C. Kim, MD, ScD, of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston, and her coauthors.

“Our paper reports a disappointingly low uptake of biosimilar infliximab since the first quarter of 2017 using claims data from a large private health plan. The main and maybe the only reason to consider using a biosimilar is cost saving,” said Dr. Kim in an interview. “Our results suggest that current modest cost savings from infliximab biosimilars in the U.S. are not sufficient to promote their widespread use.”

In the payer database study conducted by Dr. Kim and colleagues, the insurer paid similar mean amounts per patient per quarter for originator and biosimilar infliximab in mid-2017 ($8,322 versus $8,656). By the end of 2018, a gap appeared, with the insurer paying a mean quarterly per-patient sum of $8,111 for biosimilar infliximab compared with $9,535 for the branded biologic.

“The lack of market penetration and very modest price reductions for biosimilars have left policymakers, payers, physicians, and the public frustrated, particularly because sales in Europe continue to rapidly expand and robust cost-savings have materialized,” wrote Jinoos Yazdany, MD, MPH, in an editorial accompanying the study.

Dr. Yazdany, professor and chief of the division of rheumatology at the University of California, San Francisco, noted that increased spending on biologics in the United States – which increased by 50% from 2014 to 2018 – has been driven by rising prices as well as increased uptake of biologic therapies.

At least in part, Europe has been able to reap cost savings where the United States hasn’t because fundamental differences in health care reimbursement can ease sweeping biosimilar adoption, Dr. Yazdany noted. “Countries like Denmark and Sweden, using the negotiating and purchasing power of their single-payer systems have instituted a winner-takes-all bidding system,” with Denmark seeing cost savings of up to two-thirds when bidding was combined with mandatory switching, she said.

The continued market dominance of originator infliximab means that savings from biosimilars have thus far amounted to about $91 million, far short of the $1 billion that the Congressional Budget Office had projected for this date, Dr. Yazdany said.

One problem in the adoption of biosimilars by U.S. rheumatologists may have been uneven marketing and pricing across different types of practice, Colin C. Edgerton, MD, a rheumatologist at Low Country Rheumatology in South Carolina and chair of the American College of Rheumatology’s Committee on Rheumatologic Care, said in an interview.

“Rheumatologists have generally developed comfort with biosimilars, although this is not universal. The core message, that all biologics vary and that this is OK, is getting out. In general, rheumatologists also understand the problem with high drug prices and the threat to patient access,” Dr. Edgerton said. But “the early marketing and pricing focus for biosimilars seemed to be on hospitals and facilities, and this did not work effectively for community rheumatologists, where the majority of care is delivered. We have been pleased to see a manufacturer pivot toward community rheumatology where additional efforts need to be made to bend the curve on biosimilar adoption. It is critical for practices with experience using biosimilars to educate peers, and this is where networks of practicing rheumatologists are important.”

In Dr. Yazdany’s editorial, she cited four structural factors impeding biosimilar uptake and downstream savings.

First, she cites ongoing actions by pharmaceutical companies, which create a “patent thicket” that has the effect of fencing off originator biologics from biosimilars long beyond the original 12-year exclusivity period. Supporting the notion that “patent thickets” are a common strategy, Dr. Yazdany noted that almost half of the patent applications that AbbVie has filed for adalimumab (Humira) have come in after the original exclusivity period expired in 2014. Humira’s price has risen 18% yearly during this period.

The complicated role played by pharmacy benefit managers (PBMs) is another factor in slow adoption, said Dr. Yazdany: When manufacturers offer rebates to PBMs, the price of the originator biologic may be less than its biosimilar. Further, manufacturers may sign multiyear rebate agreements just before a biosimilar launch; PBMs are also sometimes threatened with the withdrawal of rebates if they offer biosimilars, she noted.

Third, prescriber inertia may also be at play, Dr. Yazdany noted, not least because patients often see little difference in out-of-pocket costs when they make the switch to a biosimilar – PBM rebates are not necessarily passed on to patients. Payers may not reimburse a biosimilar, or formularies can be built without them, influencing prescribing, and there’s usually no reimbursement incentive for biosimilar prescribing in the nonpublic sector, she said. To the contrary, infusing a drug with a higher price often means higher reimbursement for the administering clinician, since commercial insurance reimbursement is often calculated as a percent of the charge for the drug.

Further contributing to inertia is the extra time required for patient education and writing a new set of orders – all work that can’t be captured for extra reimbursement. Dr. Edgerton said that rheumatologists can talk with patients about the “nocebo effect” relating to biosimilars. “This is a phenomenon in which patients are thought to experience worsening symptoms associated with negative beliefs about biosimilars. There has been a study in Arthritis Care & Research addressing this concern. The authors found that positive framing of biosimilars led to more participants being willing to switch than negative framing. This suggests that clinicians have an important role in informing patients about biosimilars, and addressing hesitancy.”

Finally, Dr. Yazdany pointed out that for a pharmaceutical company pursuing biosimilar approval, the regulatory pathway itself can provide its own set of complications and confusion. Biosimilars are not exact molecular replicas of the originator biologic, and these differences can change efficacy and immunogenicity, and also affect stability. Hence, a company wishing to market a biosimilar has to show the Food and Drug Administration that safety and efficacy aren’t affected by a switch to biosimilar from an originator biologic. Extrapolation from one indication to another can be made – with scientific justification.

Rheumatologists are mindful of the potential differences between biosimilars and the originator biologic, as evinced in a recent position statement from the American College of Rheumatology. The position statement advises that “extrapolation should be pursued with caution,” and asks for clear labeling when biosimilars have been designated “interchangeable” with their biosimilar. Interchangeability can clear the way for pharmacy substitution of a prescribed biologic, though Dr. Yazdany noted that 40 states have passed legislation requiring prescriber notification.

The FDA is currently using postmarketing pharmacovigilance to monitor biosimilar performance in the real world, and a recent systematic review “should provide some reassurance,” wrote Dr. Yazdany, citing the study, which looked at 14,000 patients who had a total of 14 disease indications for biosimilar use. The 90-article review largely found no differences in safety, efficacy, or immunogenicity between originators and their biosimilars. Dr. Yazdany recommended greater openness to incorporating the European experience in the FDA’s ongoing reassessment.

A further way forward can come through tackling the patent thicket with the proposed bipartisan Biologic Patent Transparency Act, which would require publication of biologic patents in a one-stop publicly searchable database. Going further with legislation to address anticompetitive activity by pharmaceutical companies could shorten the runway to biosimilar launching considerably, she noted.

The complicated landscape of PBMs and rebates affects many sectors of health care, and new policy efforts are needed here as well, she said. Reimbursement strategies – and much-needed continuing medical education – can both ease prescriber unfamiliarity with biosimilars and provide incentives for their use, she concluded.

Dr. Kim concurred that change is needed before the United States is likely to reap significant economic benefit from biosimilars. “The uptake of biosimilars and their impact on overall health care cost needs to be reevaluated when we have more biosimilars available in the next 3-4 years. However, for now, it appears that substantial savings achieved in some European countries – for example, Denmark – may not be possible without systemic reform of the U.S. pharmaceutical market,” she said.

Dr. Yazdany is supported by the Alice Betts Endowed Chair in Arthritis Research, the Russel/Engleman Research Center at the University of California, San Francisco, and the National Institutes of Health. She has received independent research grants from Pfizer and Genentech and research consulting fees from Eli Lilly and AstraZeneca.

Dr. Kim’s study was supported by the division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, and Arnold Ventures. Dr. Kim has received research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Bristol-Myers Squibb, and Roche.

[email protected]

SOURCES: Kim SC et al. Arthritis Rheumatol. 2020 Jan 13. doi: 10.1002/art.41201; Yazdany J. Arthritis Rheumatol. 2020 Jan 10. doi: 10.1002/art.41203.