Asthma

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

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

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

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

PHOENIX – In a 15-month phase 4 trial, an inexpensive intervention that can be explained in a single office visit reduced severe exacerbations and improved asthma control in patient populations that suffer disproportionately from the disease. This easy-to-implement strategy achieved benefits similar to those from previous studies that prompted new treatment recommendations for moderate-to-severe asthma.

The findings were reported Feb. 26 in the Late-Breaking Oral Abstracts session at the American Academy of Allergy, Asthma, and Immunology (AAAAI) 2022 Meeting, coinciding with publication in the New England Journal of Medicine.

Black and Latino patients are under-represented in asthma research trials yet visit the emergency room and die from asthma-related complications at more than twice the rates of their White counterparts. Prior efforts to reduce this burden “have been expensive, difficult, and mostly unsuccessful,” Juan-Carlos Cardet, MD, MPH, assistant professor of internal medicine at the University of South Florida, Tampa, told attendees.

Dr. Cardet and his colleagues, led by principal investigator Elliot Israel, MD, of Brigham & Women’s Hospital, Boston, Mass., designed a study with input and financial support from the Patient-Centered Outcomes Research Institute (PCORI). The trial recruited 603 Black and 598 Latino adults with moderate-to-severe asthma. About a fifth were current or former smokers, and many lived in smoking environments. All had poorly controlled asthma or at least one severe asthma attack in the previous year. Each participant held prescriptions for daily inhaled corticosteroids (ICS) with or without long-acting beta-agonists.

Current guidelines recommend daily ICS in all but the mildest asthma cases, yet adherence is poor. Patients generally take medicine when they perceive a need, and since asthma is episodic, “most people don’t like to take controller therapy for asthma,” Dr. Cardet told this news organization in advance of his meeting presentation. Rather, many asthma patients use quick-relief therapies, such as albuterol or nebulizers, on an as-needed basis.

Prior research showed that clinical outcomes can improve with a strategy called Single Maintenance and Reliever Therapy (SMART). In this approach, an ICS (budesonide) is combined with a long-acting beta-agonist (formoterol) into a single inhaler so that patients automatically receive inhaled steroids whenever they treat their symptoms with quick-relief medication. The ICS-formoterol strategy looked promising in studies published more than a decade ago, and those results have prompted an update in national treatment guidelines, but “it’s been difficult to get [the strategy] into the clinic,” Dr. Cardet told this news organization. “FDA cautions against as-needed use of ICS-formoterol. That’s a big reason. Insurance companies won’t pay for it.”

Unlike the SMART studies, which asked participants to replace their usual controller and rescue therapies with the all-in-one inhaler, Black and Latino patients in the new trial were told to continue with their usual asthma care. On top of usual care, half of the participants were randomly assigned to receive one-time instruction around use of a controller medication (beclomethasone; Qvar) supplied by study investigators. “Essentially we told them to keep doing what your doctor tells you to do, but whenever you use a puff of rescue therapy, puff yourself with this Qvar, and if you use the nebulizer, puff yourself five times with the Qvar,” Dr. Cardet said.

This approach, called Patient Activated Reliever-Triggered Inhaled Corticosteroid (PARTICS), was explained to patients through a video in English and Spanish. “All of this we instructed in a single study visit,” Dr. Cardet said.

The PARTICS intervention reduced severe asthma exacerbations by 15% (0.13 exacerbations per patient per year) – on par with the estimated 0.12 exacerbations per patient annualized reduction with SMART. In addition, the PARTICS group had:

• better asthma control (3.4-point increase on the Asthma Control Test, vs. a 2.5-point increase in the usual-care group);
• improved quality of life (0.12-point increase on the Asthma Symptom Utility Index, vs. a 0.08-point increase in the usual-care group);
• fewer self-reported days lost from work, school, and usual activities (13.4 days, vs. 16.8 days in the usual-care group).

Addressing long-standing challenges with controller therapy compliance, this was a real-world strategy “to get more inhaled steroids in [asthma patients] on a regular basis,” Brian Vickery, MD, director of the Food Allergy Center at Emory University + Children’s Healthcare of Atlanta, said during the meeting session Q&A. Dr. Vickery was not involved in the study. “And you see an effect size that rivaled previous studies, which suggests to me that the improvement is in the inhaled steroid component and not necessarily the long-acting beta-agonist.”

The study team hopes these results can be implemented on a health care system level. “If it stays just in a journal, it’s not going to do anything. We want to help people. We want to bring it to clinic,” Dr. Cardet said in an interview.

The study was supported by a Patient-Centered Outcomes Research Institute (PCORI) award to Israel and by grants from the National Institute of Allergy and Infectious Diseases and the American Lung Association–American Academy of Allergy, Asthma, and Immunology to Dr. Cardet. QVAR and QVAR RediHaler inhalers were provided free of charge, and funding for the AssistRx pharmacy was provided by Teva Pharmaceuticals. NIOX VERO devices for measuring exhaled nitric oxide were provided free of charge by Circassia Pharmaceuticals. Dr. Cardet reported honoraria from AstraZeneca and Genentech for work in advisory boards and from GlaxoSmithKline for educational lectures on asthma, all unrelated to the AAAAI presentation. Dr. Vickery has disclosed no relevant financial relationships.

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

Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.

Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.

The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.

Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.

“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.

And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.

“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”

He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.

In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
 

Study details

The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.

Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.

The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).

Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).

The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.

This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.

Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.

Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.

The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.

Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.

“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.

And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.

“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”

He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.

In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
 

Study details

The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.

Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.

The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).

Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).

The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.

This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.

Azithromycin administered for severe early-life respiratory syncytial virus (RSV) bronchiolitis did not prevent recurrent wheezing in affected children over the next 2-4 years, a randomized, single-center study found.

Antibiotics are frequently given to patients with RSV bronchiolitis, although this practice is not supported by American Academy of Pediatrics clinical guidelines. Many doctors will prescribe them anyway if they see redness in the ears or other signs of infection, lead author Avraham Beigelman, MD, a pediatric allergist and immunologist at Washington University in St. Louis, said in an interview.

The double-blind, placebo-controlled trial, presented at the 2022 meeting of the American Academy of Allergy, Asthma & Immunology in Phoenix, was simultaneously published online Feb. 27, 2022, in the New England Journal of Medicine–Evidence.

Since azithromycin has shown anti-inflammatory benefit in chronic lung diseases and is a mainstay of care in cystic fibrosis and had shown previous effects in RSV patients, this trial examined its potential for preventing future recurrent wheezing in infants hospitalized with RSV who are at risk for developing asthma later. About half of children admitted to the hospital for RSV will develop asthma by age 7, Dr. Beigelman said.

“We were very surprised that azithromycin didn’t help in this trial given our previous findings,” Dr. Beigelman said.

And while those given azithromycin versus those given a placebo showed no significant decrease in recurrent wheezing, there was a slight suggestion that treatment with antibiotics of any kind may increase the risk of later wheezing in infants hospitalized with the virus.

“The study was not designed to tease at the effects of different antibiotics or combinations of antibiotics, so we have to be very cautious about this trend,” Dr. Beigelman said. “There may be short-term effects and long-term effects. Certain antibiotics may affect the infant microbiome in other parts of the body, such as the gut, [in] a way that may predispose to asthma. But all these associations suggest that early-life antibiotics for viral infections are not good for you.”

He pointed to the longstanding question among clinicians whether it is the antibiotic that’s increasing the risk of the harm or the condition for which the antibiotic is prescribed. These exploratory data, however, suggest that antibiotics for RSV may be causing harm.

In pursuit of that hypothesis, his group has collected airway microbiome samples from these infants and plan to investigate whether bacteria colonizing the airway may interact with the antibiotics to increase wheezing. The researchers will analyze stool samples from the babies to see whether the gut microbiome may also play a role in wheezing and the subsequent risk of developing childhood asthma.
 

Study details

The trial prospectively enrolled 200 otherwise healthy babies aged 1-18 months who were hospitalized at St. Louis Children’s Hospital for acute RSV bronchiolitis. Although RSV is a very common pediatric virus, only bout 3% of babies will require hospitalization in order to receive oxygen, Dr. Beigelman said.

Babies were randomly assigned to receive placebo or oral azithromycin at 10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days. Randomization was stratified by recent open-label antibiotic use. The primary outcome was recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2-4 years.

The biologic activity of azithromycin was clear since nasal-wash interleukin at day 14 after randomization was lower in azithromycin-treated infants. But despite evidence of activity, the risk of post-RSV recurrent wheeze was similar in both arms: 47% in the azithromycin group versus 36% in the placebo group, for an adjusted hazard ratio of 1.45 (95% confidence interval, 0.92-2.29; P = .11).

Nor did azithromycin lower the risk of recurrent wheeze in babies already receiving other antibiotics at the time of enrollment (HR, 0.94; 95% CI, 0.43-2.07). As for antibiotic-naive participants receiving azithromycin, there was a slight signal of potential increased risk of developing recurrent wheezing (HR, 1.79; 95% CI, 1.03-3.1).

The bottom line? The findings support current clinical guidelines recommending against the use of antibiotics for RSV. “At the very least, azithromycin and antibiotics in general have no benefit in preventing recurrent wheeze, and there is a possibility they may be harmful,” Dr. Beigelman said.

This trial is funded by the National Heart, Lung, and Blood Institute. Dr. Beigelman reported relationships with AstraZeneca, Novartis, and Sanofi. Two study coauthors disclosed various ties to industry.

Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.” 

Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.

Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).

Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall. 

Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.

Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.

“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”

Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.

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

Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.” 

Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.

Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).

Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall. 

Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.

Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.

“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”

Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.

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

Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.” 

Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.

Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).

Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall. 

Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.

Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.

“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”

Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.

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

Bronchiolitis is the leading cause of infant hospitalizations in the United States and Europe, and almost one-third of these patients go on to develop asthma later in childhood.

But a multinational team of researchers has presented evidence that could avoid that outcome. They identified four different subtypes of bronchiolitis along with a decision tree that can determine which infants are most likely to develop asthma as they get older.

Reporting in the journal eClinical Medicine, Michimasa Fujiogi, MD, of Massachusetts General Hospital and Harvard University, Boston, and colleagues analyzed three multicenter prospective cohort studies that included a combined 3,081 infants hospitalized with severe bronchiolitis.

“This study added a base for the early identification of high-risk patients during early infancy,” Dr. Fujiogi said in an interview. “Using the prediction rule of this study, it is possible to identify groups at high risk of asthma during a critical period of airway development – early infancy.”

The researchers identified four clinically distinct and reproducible profiles of infants hospitalized for bronchiolitis:

• A: characterized by a history of breathing problems and eczema, rhinovirus infection, and low prevalence of respiratory syncytial virus (RSV) infection.
• B: characterized by the classic symptoms of wheezing and cough at presentation, a low prevalence of previous breathing problems and rhinovirus infection, and a high likelihood of RSV infection.
• C: the most severe group, characterized by inadequate oral intake, severe retraction at presentation, and longer hospital stays.
• D: the least ill group, with little history of breathing problems but inadequate oral intake with no or mild retraction.

Infants with profile A had the highest risk for developing asthma – more than 250% greater than with typical bronchiolitis. They were also older and were more likely to have parents who had asthma – and none had solo-RSV infection. In the overall analysis, the risk for developing asthma by age 6 or 7 was 23%.

The researchers stated that the decision tree accurately predicts the high-risk profile with high degrees of sensitivity and specificity. The decision tree used four predictors that together defined infants with profile A: RSV infection status, previous breathing problems, eczema, and parental asthma.

“Our data would facilitate the development of profile-specific prevention strategies for asthma – for example, modification of host response, prophylaxis for severe viral infection – by identifying asthma risk groups early in infancy,” Dr. Fujiogi said.

The study received funding from the National Institutes of Health. Dr. Fujiogi and coauthors have disclosed no relevant financial relationships.

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

Bronchiolitis is the leading cause of infant hospitalizations in the United States and Europe, and almost one-third of these patients go on to develop asthma later in childhood.

But a multinational team of researchers has presented evidence that could avoid that outcome. They identified four different subtypes of bronchiolitis along with a decision tree that can determine which infants are most likely to develop asthma as they get older.

Reporting in the journal eClinical Medicine, Michimasa Fujiogi, MD, of Massachusetts General Hospital and Harvard University, Boston, and colleagues analyzed three multicenter prospective cohort studies that included a combined 3,081 infants hospitalized with severe bronchiolitis.

“This study added a base for the early identification of high-risk patients during early infancy,” Dr. Fujiogi said in an interview. “Using the prediction rule of this study, it is possible to identify groups at high risk of asthma during a critical period of airway development – early infancy.”

The researchers identified four clinically distinct and reproducible profiles of infants hospitalized for bronchiolitis:

• A: characterized by a history of breathing problems and eczema, rhinovirus infection, and low prevalence of respiratory syncytial virus (RSV) infection.
• B: characterized by the classic symptoms of wheezing and cough at presentation, a low prevalence of previous breathing problems and rhinovirus infection, and a high likelihood of RSV infection.
• C: the most severe group, characterized by inadequate oral intake, severe retraction at presentation, and longer hospital stays.
• D: the least ill group, with little history of breathing problems but inadequate oral intake with no or mild retraction.

Infants with profile A had the highest risk for developing asthma – more than 250% greater than with typical bronchiolitis. They were also older and were more likely to have parents who had asthma – and none had solo-RSV infection. In the overall analysis, the risk for developing asthma by age 6 or 7 was 23%.

The researchers stated that the decision tree accurately predicts the high-risk profile with high degrees of sensitivity and specificity. The decision tree used four predictors that together defined infants with profile A: RSV infection status, previous breathing problems, eczema, and parental asthma.

“Our data would facilitate the development of profile-specific prevention strategies for asthma – for example, modification of host response, prophylaxis for severe viral infection – by identifying asthma risk groups early in infancy,” Dr. Fujiogi said.

The study received funding from the National Institutes of Health. Dr. Fujiogi and coauthors have disclosed no relevant financial relationships.

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

Bronchiolitis is the leading cause of infant hospitalizations in the United States and Europe, and almost one-third of these patients go on to develop asthma later in childhood.

But a multinational team of researchers has presented evidence that could avoid that outcome. They identified four different subtypes of bronchiolitis along with a decision tree that can determine which infants are most likely to develop asthma as they get older.

Reporting in the journal eClinical Medicine, Michimasa Fujiogi, MD, of Massachusetts General Hospital and Harvard University, Boston, and colleagues analyzed three multicenter prospective cohort studies that included a combined 3,081 infants hospitalized with severe bronchiolitis.

“This study added a base for the early identification of high-risk patients during early infancy,” Dr. Fujiogi said in an interview. “Using the prediction rule of this study, it is possible to identify groups at high risk of asthma during a critical period of airway development – early infancy.”

The researchers identified four clinically distinct and reproducible profiles of infants hospitalized for bronchiolitis:

• A: characterized by a history of breathing problems and eczema, rhinovirus infection, and low prevalence of respiratory syncytial virus (RSV) infection.
• B: characterized by the classic symptoms of wheezing and cough at presentation, a low prevalence of previous breathing problems and rhinovirus infection, and a high likelihood of RSV infection.
• C: the most severe group, characterized by inadequate oral intake, severe retraction at presentation, and longer hospital stays.
• D: the least ill group, with little history of breathing problems but inadequate oral intake with no or mild retraction.

Infants with profile A had the highest risk for developing asthma – more than 250% greater than with typical bronchiolitis. They were also older and were more likely to have parents who had asthma – and none had solo-RSV infection. In the overall analysis, the risk for developing asthma by age 6 or 7 was 23%.

The researchers stated that the decision tree accurately predicts the high-risk profile with high degrees of sensitivity and specificity. The decision tree used four predictors that together defined infants with profile A: RSV infection status, previous breathing problems, eczema, and parental asthma.

“Our data would facilitate the development of profile-specific prevention strategies for asthma – for example, modification of host response, prophylaxis for severe viral infection – by identifying asthma risk groups early in infancy,” Dr. Fujiogi said.

The study received funding from the National Institutes of Health. Dr. Fujiogi and coauthors have disclosed no relevant financial relationships.

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

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than were those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7,000 individuals.

“Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage,” wrote Rotem Lapidot, MD, of Boston University, and colleagues. Previous research has linked pneumonia with subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the impact of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine , the researchers identified 1,343 infants who had CAP in the first 2 years of life, and 6,715 controls, using a large electronic health records dataset (Optum EHR dataset) for the period from Jan. 2011 through June 2018.

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the CAP patients and controls.
 

Future risk

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for CAP patients versus 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 versus 1.9 per 100 patient-years (RR, 3.2) and 1.0 versus 0.2 per 100 patient-years (RR, 6.3) for the CAP patients and controls, respectively.

The distribution of CAP etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the CAP patients had only one qualifying hospitalization for CAP before 2 years of age, and the mean age at the first hospitalization was 8.9 months. “Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred,” and were highest for children hospitalized at close to 2 years of age, the researchers noted.
 

Persistent inflammation?

“Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease,” the researchers wrote.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP, and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they said. “Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae,” they concluded.

Dr. Lapidot and several coauthors disclosed ties with Pfizer, the study sponsor.

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

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than were those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7,000 individuals.

“Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage,” wrote Rotem Lapidot, MD, of Boston University, and colleagues. Previous research has linked pneumonia with subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the impact of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine , the researchers identified 1,343 infants who had CAP in the first 2 years of life, and 6,715 controls, using a large electronic health records dataset (Optum EHR dataset) for the period from Jan. 2011 through June 2018.

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the CAP patients and controls.
 

Future risk

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for CAP patients versus 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 versus 1.9 per 100 patient-years (RR, 3.2) and 1.0 versus 0.2 per 100 patient-years (RR, 6.3) for the CAP patients and controls, respectively.

The distribution of CAP etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the CAP patients had only one qualifying hospitalization for CAP before 2 years of age, and the mean age at the first hospitalization was 8.9 months. “Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred,” and were highest for children hospitalized at close to 2 years of age, the researchers noted.
 

Persistent inflammation?

“Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease,” the researchers wrote.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP, and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they said. “Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae,” they concluded.

Dr. Lapidot and several coauthors disclosed ties with Pfizer, the study sponsor.

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

Preschoolers who experienced community-acquired pneumonia in infancy were significantly more likely than were those with no history of pneumonia to develop chronic respiratory disorders, based on data from approximately 7,000 individuals.

“Lower respiratory tract infections (LRTI) during the first years of life cause injury to the rapidly developing lung at its most critical stage,” wrote Rotem Lapidot, MD, of Boston University, and colleagues. Previous research has linked pneumonia with subsequent chronic cough, bronchitis, and recurrent pneumonia in children, but data are needed to assess the impact of early community-acquired pneumonia (CAP) on respiratory health in otherwise healthy infants, the researchers said.

In a retrospective matched cohort study published in Respiratory Medicine , the researchers identified 1,343 infants who had CAP in the first 2 years of life, and 6,715 controls, using a large electronic health records dataset (Optum EHR dataset) for the period from Jan. 2011 through June 2018.

The primary outcomes were the development of any chronic respiratory disorders, reactive airway disease, and CAP hospitalizations between ages 2 and 5 years. Infants in the CAP group were otherwise healthy; those with congenital or other conditions that might predispose them to pneumonia were excluded. Baseline characteristics were similar between the CAP patients and controls.
 

Future risk

Overall, the rates per 100 patient-years for any chronic respiratory disorder were 11.6 for CAP patients versus 4.9 for controls (relative risk, 2.4). Rates for reactive airway disease and CAP hospitalization were 6.1 versus 1.9 per 100 patient-years (RR, 3.2) and 1.0 versus 0.2 per 100 patient-years (RR, 6.3) for the CAP patients and controls, respectively.

The distribution of CAP etiology of CAP in infants at the first hospitalization was 20% bacterial, 27% viral, and 53% unspecified. The relative rates of later respiratory illness were similar across etiologies of the initial hospitalization for CAP, which support the association between infant CAP and later respiratory disease, the researchers said.

Nearly all (97%) of the CAP patients had only one qualifying hospitalization for CAP before 2 years of age, and the mean age at the first hospitalization was 8.9 months. “Rates and relative rates of any chronic respiratory disorder, and our composite for reactive airway disease, increased with age at which the initial CAP hospitalization occurred,” and were highest for children hospitalized at close to 2 years of age, the researchers noted.
 

Persistent inflammation?

“Our findings add to the evolving hypothesis that persistent inflammation following pneumonia creates an increased risk for subsequent respiratory disease and exacerbations of underlying disease,” the researchers wrote.

The study findings were limited by several factors, including the potential for misclassification of some infants with and without underlying conditions, reliance on discharge information for etiology, and possible lack of generalizability to other populations, the researchers noted.

However, the results indicate an increased risk for respiratory illness in early childhood among infants with CAP, and support the need for greater attention to CAP prevention and for strategies to reduce inflammation after pneumonia, they said. “Further study is needed to confirm the long-term consequences of infant CAP and the underlying mechanisms that lead to such long-term sequelae,” they concluded.

Dr. Lapidot and several coauthors disclosed ties with Pfizer, the study sponsor.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

Use of a leukotriene receptor antagonist (LTRA) for asthma management did not increase the risk of neuropsychiatric disease, based on data from more than 60,000 asthma patients.

Although LTRAs are established as an effective drug for asthma, the U.S. Food and Drug Administration warnings of the risk for neuropsychiatric (NP) drug reactions – including a boxed warning for montelukast (Singulair) – has raised concerns, writes Ji-Su Shim, MD, of Ewha Womans University, Seoul, South Korea, and colleagues.

However, evidence for such an association is limited, and previous studies have focused only on children and adolescents, and on a single LTRA (montelukast), the researchers say.

In a study published Dec. 1 in the Journal of Allergy and Clinical Immunology: In Practice, the researchers used a Korean national health insurance database to identify 61,571 adult patients with asthma aged 40 years and older between Jan. 2002 and Dec. 2015 with no history of LTRA use.

The patients underwent screening examinations between Jan. 2009 and Dec. 2010, which marked the start of a follow-up period ending on Dec. 31, 2015. The median age of the study population was 61 years, and the mean follow-up period for NPs or other outcomes was approximately 47.6 months for LTRA users and 46.5 months for nonusers. Overall, 11.1% of the study population used pranlukast (Onon), 11% used montelukast, and 0.24% used zafirlukast (Accolate).

A total of 12,168 patients took an LTRA during the follow-up period. The hazard ratio for newly diagnosed neuropsychiatric diseases was not significantly different between LTRA users and nonusers (hazard ratio, 1.01; P = .952) in an adjusted model that included age, sex, pack-years of smoking, alcohol use, physical activity, body mass index, comorbid conditions, other respiratory diseases, and use of other asthma medications.

The most common NPs were dementia, mood disorders, and panic disorders, and the prevalence of each was not significantly different between LTRA users and nonusers (75.4% vs. 76.1% for dementia, 12.7% vs. 12.8% for mood disorders, and 5.6% vs. 3.5% for panic disorders).

A subgroup analysis for associations between the duration of LTRA use and NP disease risk also showed no significant difference between LTRA users and nonusers.

“The mechanism of the development of NP symptoms by LTRAs has not been identified,” the researchers write in their discussion of the study findings. “Because most of NP side effects due to montelukast occur in few patients within 2 weeks of drug administration, it also may have relation with the presence of some genetic polymorphisms involving modification of the normal action or metabolism of LTRAs,” they explained.

The FDA’s boxed warning for montelukast noting the risk of serious mental health side effects has renewed interest in the relationship between NPs and LTRAs, the researchers noted. However, the current study findings support previous randomized controlled trials and larger studies, and the current warnings are based mainly on pharmacovigilance studies, case series, and case reports, they said.

The study findings were limited by several factors, including the retrospective design, the potential for misclassification of asthma diagnosis, the exclusion of temporary NP symptoms that might prompt LTRA discontinuation, and the inability to detect possible differences in ethnicities other than Korean, the researchers note.

However, the results suggest that adverse NP symptoms should not prevent physicians from prescribing LTRAs to selected patients with asthma. Instead, the physician should accompany the prescription with “a word of caution in case any mood changes might occur,” the investigators wrote.

“Further studies, such as randomized controlled trials, are needed to reveal the association between the use of LTRAs and the risk of NP events and/or diseases,” they concluded.

Potential genetic predisposition may drive cases

The relatively rare occurrence of NP symptoms in asthma patients using LTRAs has prompted questions from the medical community on whether the relationship really exists, writes Désirée Larenas-Linnemann, MD, of Médica Sur Clinical Foundation and Hospital, Mexico City, in an accompanying editorial ).

The current study provides information about medications and possible adverse drug reactions, but “great care should be taken in the interpretation of the results from such a study,” she notes. Limitations include not only the possible misclassification of asthma and the homogeneous study population, but also the fact that some NPs, such as dementia, are already common in older adults..

Dr. Larenas-Linnemann shared a story of one of her patients, a 2½-year-old boy who began exhibiting hyperactivity and other strange behaviors while on an LRTA. The toddler’s father had previously reported “horrible nightmares, strange thoughts, and to feel upset, unsecure until he suspended the medication.” Cases such as this support a potential genetic predisposition, with drug metabolism playing a role, and clinicians should take genetic backgrounds into account, she said.

“Even though the current study did not show an association between LTRA use or duration of exposure and the occurrence of NP diseases in Korean adults with asthma, this does not imply such a relationship might be present in other age groups (children-adolescents-adults up to 50 years) or in patients with a different genetic background,” she emphasized.

However, “In the meantime, although LTRA should continue to be prescribed if indicated, an index of suspicion for possible NP effects should be maintained,” Dr. Larenas-Linnemann concluded.

“This study is timely, since the boxed warning for montelukast was issued approximately 1 year ago by the FDA,” Thomas B. Casale, MD, of the University of South Florida, Tampa, said in an interview.

Dr. Casale said he was not surprised by the findings, “since most of the data implicating a potential link between the use of montelukast and neuropsychiatric disorders have not been particularly compelling,” and much of the current information comes from case reports and retrospective studies.

“Furthermore, the data appeared to be somewhat stronger in the pediatric population,” Dr. Casale noted. “This study focused on elderly patients (mean age 61) and included two other leukotriene modifiers. The number of patients receiving montelukast was small (56), which may have also confounded the results,” he noted.

As for clinical implications, “I don’t think this study will change practice,” Dr. Casale said. “As indicated, it is in an elderly population, included only a limited number of patients receiving montelukast, and was in a Korean cohort. All of these factors could have influenced the results,” and the data may not be generalizable to patients elsewhere, including the United States, he said. “Also, the study only included patients with asthma and in the United States; the approval for rhinitis is another important indication to study,” he noted.

Additional research is needed in the form of better prospective studies examining the potential link between montelukast and neuropsychiatric disorders in both the pediatric and adult populations having either asthma or rhinitis, Dr. Casale concluded.

The study received no outside funding. The researchers and Dr. Casale have disclosed no relevant financial relationships. Dr. Larenas-Linnemann disclosed personal fees from Allakos, Armstrong, AstraZeneca, Chiesi, DBV Technologies, Grünenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, and Carnot, and grants from Sanofi, AstraZeneca, Novartis, Circassia, UCB, GSK, and the Purina Institute.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

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

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

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

The Food and Drug Administration has approved tezepelumab-ekko (Tezspire) as a first-in-class treatment for severe asthma in adults and pediatric patients aged 12 years and older. It is not recommended for the relief of acute bronchospasm or status asthmaticus.
 

Tezepelumab-ekko is a human monoclonal antibody that acts as a thymic stromal lymphopoietin (TSLP) blocker. TSLP is an epithelial cell–derived cytokine implicated in the pathogenesis of asthma. Tezepelumab-ekko is administered by subcutaneous injection at a recommended dosage of 210 mg given once every 4 weeks.

“Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma,” said professor Andrew Menzies-Gow, MD, PhD, director of the lung division, Royal Brompton Hospital, London, and the principal investigator of the pivotal NAVIGATOR trial, in a Dec. 17 Amgen press release.
 

Trial results

The early approval of the treatment was based on the results of various clinical trials, primarily the NAVIGATOR phase 3 trial, results of which were published in the New England Journal of Medicine in May 2021.

In the NAVIGATOR trial, a total of 1,061 patients were randomly assigned to receive tezepelumab (529 patients) or placebo (532 patients).

With tezepelumab, the annualized rate of asthma exacerbations was 0.93; with placebo, the rate was 2.10 (P < .001).

“Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo,” according to the report of NAVIGATOR trial, which was funded by AstraZeneca and Amgen.
 

Tezepelumab details

The full prescribing information for tezepelumab-ekko is available, including specific warnings and areas of concern where information is not available. The drug should not be administered to individuals with known hypersensitivity to tezepelumab-ekko or excipients, and hypersensitivity reactions (e.g., rash and allergic conjunctivitis), can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

The drug should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus, and the use of live-attenuated vaccines in patients receiving tezepelumab-ekko should be avoided.

There is no available data regarding the use of tezepelumab-ekko in patients who are pregnant, although placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy, according to the company.

The most common adverse reactions for the drug, with a reported incidence of at least 3%, are pharyngitis, arthralgia, and back pain.

“The approval of Tezspire is long-awaited positive news for the asthma community,” said Tonya Winders, president and CEO at the Allergy & Asthma Network and president of the Global Allergy and Airways Patient Platform in the Amgen press release. “For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation.”

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