Asthma

The Food and Drug Administration has approved a generic version of the Advair Diskus, a complex device-drug combination containing fluticasone propionate and salmeterol inhalation powder.

The generic device will be available in three strengths: fluticasone propionate 100 mcg/ salmeterol 50 mcg, fluticasone propionate 250 mcg/ salmeterol 50 mcg and fluticasone propionate 500 mcg/ salmeterol 50 mcg, according to the FDA announcement. It will be marketed by Mylan as Wixela Inhub and will launch in late February, according to a statement from Mylan.

Advair Diskus is among the most commonly used treatments for asthma and for chronic obstructive pulmonary disease (COPD), so it’s hoped this approval will increase access to the therapy, FDA officials said in a statement.

This approval is part of the FDA’s “longstanding commitment to advance access to lower cost, high quality generic alternatives,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement. “People living with asthma and COPD know too well the critical importance of having access to the treatment they need to feel better. Today’s approval will bring more competition to the market which will ultimately benefit the patients who rely on this drug.”

Wixela Inhub is indicated for twice-daily treatment of asthma in patients aged 4 years and older who are not adequately controlled by long-term asthma control treatments or whose disease warrants treatment with a combination of inhaled corticosteroids and long-acting beta agonists. It also is indicated for maintenance of COPD and reduction of COPD exacerbations.

cpalmer@mdedge.com

The Food and Drug Administration has approved a generic version of the Advair Diskus, a complex device-drug combination containing fluticasone propionate and salmeterol inhalation powder.

The generic device will be available in three strengths: fluticasone propionate 100 mcg/ salmeterol 50 mcg, fluticasone propionate 250 mcg/ salmeterol 50 mcg and fluticasone propionate 500 mcg/ salmeterol 50 mcg, according to the FDA announcement. It will be marketed by Mylan as Wixela Inhub and will launch in late February, according to a statement from Mylan.

Advair Diskus is among the most commonly used treatments for asthma and for chronic obstructive pulmonary disease (COPD), so it’s hoped this approval will increase access to the therapy, FDA officials said in a statement.

This approval is part of the FDA’s “longstanding commitment to advance access to lower cost, high quality generic alternatives,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement. “People living with asthma and COPD know too well the critical importance of having access to the treatment they need to feel better. Today’s approval will bring more competition to the market which will ultimately benefit the patients who rely on this drug.”

Wixela Inhub is indicated for twice-daily treatment of asthma in patients aged 4 years and older who are not adequately controlled by long-term asthma control treatments or whose disease warrants treatment with a combination of inhaled corticosteroids and long-acting beta agonists. It also is indicated for maintenance of COPD and reduction of COPD exacerbations.

cpalmer@mdedge.com

The Food and Drug Administration has approved a generic version of the Advair Diskus, a complex device-drug combination containing fluticasone propionate and salmeterol inhalation powder.

The generic device will be available in three strengths: fluticasone propionate 100 mcg/ salmeterol 50 mcg, fluticasone propionate 250 mcg/ salmeterol 50 mcg and fluticasone propionate 500 mcg/ salmeterol 50 mcg, according to the FDA announcement. It will be marketed by Mylan as Wixela Inhub and will launch in late February, according to a statement from Mylan.

Advair Diskus is among the most commonly used treatments for asthma and for chronic obstructive pulmonary disease (COPD), so it’s hoped this approval will increase access to the therapy, FDA officials said in a statement.

This approval is part of the FDA’s “longstanding commitment to advance access to lower cost, high quality generic alternatives,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a statement. “People living with asthma and COPD know too well the critical importance of having access to the treatment they need to feel better. Today’s approval will bring more competition to the market which will ultimately benefit the patients who rely on this drug.”

Wixela Inhub is indicated for twice-daily treatment of asthma in patients aged 4 years and older who are not adequately controlled by long-term asthma control treatments or whose disease warrants treatment with a combination of inhaled corticosteroids and long-acting beta agonists. It also is indicated for maintenance of COPD and reduction of COPD exacerbations.

cpalmer@mdedge.com

I appreciated the PURL, “Should you reassess your patient’s asthma diagnosis?” (J Fam Pract. 2018;67:704-707) that reminded clinicians to taper asthma controller medications in asymptomatic patients. The articles cited^1,2 by Drs. Stevermer and Hayes documented that one-third of the adults enrolled in the respective study with physician-diagnosed asthma did not have objective evidence for asthma and were either over-diagnosed or had remitted. These articles also contained evidence that: 1) over-diagnosis was likely much more common than remission,¹ and 2) there was a significant temporal trend towards increasing over-diagnosis/remission during the last several decades. The authors of the cited article¹ suggested that the temporal trend could be explained by increased public awareness of respiratory symptoms, more aggressive marketing of asthma medications, and a lack of objective measurement of reversible airway obstruction in primary care. These assertions deserve careful consideration as we strive to diagnose asthma appropriately.

Over-diagnosis/remission is almost certainly not as prevalent (33%) as the authors of the cited articles^1,2 reported. The reason is simple selection bias: 1) the cited study² excluded asthma patients who smoked >10 pack-years (it enrolled 701 asthma patients and excluded 812 asthma patients with a >10 pack-year smoking history), and 2) this study likely did not include asthma patients with the asthma-COPD overlap syndrome, which is treated as asthma and comprises an additional 30% of our patients with chronic airflow limitation (the asthma-COPD spectrum).³ Asthma patients who smoke and/or have the overlap syndrome are prone to severe asthma that is refractory to inhaled corticosteroids.^3,4

In addition to making the correct diagnosis, it is equally important to be aware of efficacious therapies for severe refractory asthma that primary care clinicians can easily use. There is now good evidence that azithromycin is efficacious for severe refractory asthma⁵ and should be considered prior to referral for immunomodulatory asthma therapies.⁶

David L. Hahn, MD, MS
Madison, Wis

1. Aaron SD, Vandemheen KL, Boulet LP, et al; Canadian Respiratory Clinical Research Consortium. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008;179:1121-1131.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

3. Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax. 2009;64:728-735.

4. Stapleton M, Howard-Thompson A, George C, et al. Smoking and asthma. J Am Board Fam Med. 2011;24;313-322.

5. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017:390659-668.

6. Hahn DL, Grasmick M, Hetzel S, et al; AZMATICS (AZithroMycin-Asthma Trial In Community Settings) Study Group. Azithromycin for bronchial asthma in adults: an effectiveness trial. J Am Board Fam Med. 2012;25:442-459.

Continue to: Authors' response...

Authors’ response:

We appreciate Dr. Hahn’s observations about the PURL¹ on overdiagnosis of asthma. This article focused on the results of a prospective, multicenter cohort study² that evaluated the feasibility of tapering, and in many patients, stopping asthma medications. We agree that if the study had included people diagnosed with asthma who also had smoked at least 10 pack-years or who also had COPD, the proportion of those who would eventually no longer meet diagnostic criteria for asthma would be lower than in this study. We are uncertain of the relative proportion of cases that were overdiagnosis, when compared with true remission of disease, as only 43% of those no longer meeting the diagnostic criteria for asthma had evidence of prior lung function testing, whether by formal spirometry, serial peak function testing, or bronchial challenge testing.

We agree that using efficacious therapies for severe refractory asthma is essential, but the selection of those therapies was outside the scope of this PURL.

James J. Stevermer, MD, MSPH; Alisa Hayes, MD
Columbia, Mo

1. Stevermer JJ, Hayes A. Should you reassess your patient’s asthma diagnosis? J Fam Pract. 2018;67:704-707.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

I appreciated the PURL, “Should you reassess your patient’s asthma diagnosis?” (J Fam Pract. 2018;67:704-707) that reminded clinicians to taper asthma controller medications in asymptomatic patients. The articles cited^1,2 by Drs. Stevermer and Hayes documented that one-third of the adults enrolled in the respective study with physician-diagnosed asthma did not have objective evidence for asthma and were either over-diagnosed or had remitted. These articles also contained evidence that: 1) over-diagnosis was likely much more common than remission,¹ and 2) there was a significant temporal trend towards increasing over-diagnosis/remission during the last several decades. The authors of the cited article¹ suggested that the temporal trend could be explained by increased public awareness of respiratory symptoms, more aggressive marketing of asthma medications, and a lack of objective measurement of reversible airway obstruction in primary care. These assertions deserve careful consideration as we strive to diagnose asthma appropriately.

Over-diagnosis/remission is almost certainly not as prevalent (33%) as the authors of the cited articles^1,2 reported. The reason is simple selection bias: 1) the cited study² excluded asthma patients who smoked >10 pack-years (it enrolled 701 asthma patients and excluded 812 asthma patients with a >10 pack-year smoking history), and 2) this study likely did not include asthma patients with the asthma-COPD overlap syndrome, which is treated as asthma and comprises an additional 30% of our patients with chronic airflow limitation (the asthma-COPD spectrum).³ Asthma patients who smoke and/or have the overlap syndrome are prone to severe asthma that is refractory to inhaled corticosteroids.^3,4

In addition to making the correct diagnosis, it is equally important to be aware of efficacious therapies for severe refractory asthma that primary care clinicians can easily use. There is now good evidence that azithromycin is efficacious for severe refractory asthma⁵ and should be considered prior to referral for immunomodulatory asthma therapies.⁶

David L. Hahn, MD, MS
Madison, Wis

1. Aaron SD, Vandemheen KL, Boulet LP, et al; Canadian Respiratory Clinical Research Consortium. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008;179:1121-1131.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

3. Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax. 2009;64:728-735.

4. Stapleton M, Howard-Thompson A, George C, et al. Smoking and asthma. J Am Board Fam Med. 2011;24;313-322.

5. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017:390659-668.

6. Hahn DL, Grasmick M, Hetzel S, et al; AZMATICS (AZithroMycin-Asthma Trial In Community Settings) Study Group. Azithromycin for bronchial asthma in adults: an effectiveness trial. J Am Board Fam Med. 2012;25:442-459.

Continue to: Authors' response...

Authors’ response:

We appreciate Dr. Hahn’s observations about the PURL¹ on overdiagnosis of asthma. This article focused on the results of a prospective, multicenter cohort study² that evaluated the feasibility of tapering, and in many patients, stopping asthma medications. We agree that if the study had included people diagnosed with asthma who also had smoked at least 10 pack-years or who also had COPD, the proportion of those who would eventually no longer meet diagnostic criteria for asthma would be lower than in this study. We are uncertain of the relative proportion of cases that were overdiagnosis, when compared with true remission of disease, as only 43% of those no longer meeting the diagnostic criteria for asthma had evidence of prior lung function testing, whether by formal spirometry, serial peak function testing, or bronchial challenge testing.

We agree that using efficacious therapies for severe refractory asthma is essential, but the selection of those therapies was outside the scope of this PURL.

James J. Stevermer, MD, MSPH; Alisa Hayes, MD
Columbia, Mo

1. Stevermer JJ, Hayes A. Should you reassess your patient’s asthma diagnosis? J Fam Pract. 2018;67:704-707.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

I appreciated the PURL, “Should you reassess your patient’s asthma diagnosis?” (J Fam Pract. 2018;67:704-707) that reminded clinicians to taper asthma controller medications in asymptomatic patients. The articles cited^1,2 by Drs. Stevermer and Hayes documented that one-third of the adults enrolled in the respective study with physician-diagnosed asthma did not have objective evidence for asthma and were either over-diagnosed or had remitted. These articles also contained evidence that: 1) over-diagnosis was likely much more common than remission,¹ and 2) there was a significant temporal trend towards increasing over-diagnosis/remission during the last several decades. The authors of the cited article¹ suggested that the temporal trend could be explained by increased public awareness of respiratory symptoms, more aggressive marketing of asthma medications, and a lack of objective measurement of reversible airway obstruction in primary care. These assertions deserve careful consideration as we strive to diagnose asthma appropriately.

Over-diagnosis/remission is almost certainly not as prevalent (33%) as the authors of the cited articles^1,2 reported. The reason is simple selection bias: 1) the cited study² excluded asthma patients who smoked >10 pack-years (it enrolled 701 asthma patients and excluded 812 asthma patients with a >10 pack-year smoking history), and 2) this study likely did not include asthma patients with the asthma-COPD overlap syndrome, which is treated as asthma and comprises an additional 30% of our patients with chronic airflow limitation (the asthma-COPD spectrum).³ Asthma patients who smoke and/or have the overlap syndrome are prone to severe asthma that is refractory to inhaled corticosteroids.^3,4

In addition to making the correct diagnosis, it is equally important to be aware of efficacious therapies for severe refractory asthma that primary care clinicians can easily use. There is now good evidence that azithromycin is efficacious for severe refractory asthma⁵ and should be considered prior to referral for immunomodulatory asthma therapies.⁶

David L. Hahn, MD, MS
Madison, Wis

1. Aaron SD, Vandemheen KL, Boulet LP, et al; Canadian Respiratory Clinical Research Consortium. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008;179:1121-1131.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

3. Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax. 2009;64:728-735.

4. Stapleton M, Howard-Thompson A, George C, et al. Smoking and asthma. J Am Board Fam Med. 2011;24;313-322.

5. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017:390659-668.

6. Hahn DL, Grasmick M, Hetzel S, et al; AZMATICS (AZithroMycin-Asthma Trial In Community Settings) Study Group. Azithromycin for bronchial asthma in adults: an effectiveness trial. J Am Board Fam Med. 2012;25:442-459.

Continue to: Authors' response...

Authors’ response:

We appreciate Dr. Hahn’s observations about the PURL¹ on overdiagnosis of asthma. This article focused on the results of a prospective, multicenter cohort study² that evaluated the feasibility of tapering, and in many patients, stopping asthma medications. We agree that if the study had included people diagnosed with asthma who also had smoked at least 10 pack-years or who also had COPD, the proportion of those who would eventually no longer meet diagnostic criteria for asthma would be lower than in this study. We are uncertain of the relative proportion of cases that were overdiagnosis, when compared with true remission of disease, as only 43% of those no longer meeting the diagnostic criteria for asthma had evidence of prior lung function testing, whether by formal spirometry, serial peak function testing, or bronchial challenge testing.

We agree that using efficacious therapies for severe refractory asthma is essential, but the selection of those therapies was outside the scope of this PURL.

James J. Stevermer, MD, MSPH; Alisa Hayes, MD
Columbia, Mo

1. Stevermer JJ, Hayes A. Should you reassess your patient’s asthma diagnosis? J Fam Pract. 2018;67:704-707.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

CORONADO, CALIF. – Eosinophilic chronic rhinosinusitis with nasal polyposis decreases quality of life improvement after sinus surgery in patients with concurrent asthma, results from a retrospective study demonstrated.

They also have significantly higher Lund-Kennedy endoscopy and Lund-McKay CT scores, compared with control groups.

“Patients with concurrent asthma and chronic sinusitis require more aggressive management than nonasthmatics,” one of the study authors, Aykut A. Unsal, DO, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “Additionally, the degree of improvement of not only their sinusitis but possibly their asthma following medical/surgical treatment will also be limited if that patient also suffers from nasal polyps and/or eosinophilia. These patients will ultimately become more difficult to manage.”

In order to examine the relationship of eosinophilia and nasal polyps on quality of life (QOL) in patients with asthma who have chronic rhinosinusitis (CRS) who were treated with surgery, Dr. Unsal and his associates reviewed the records of 457 patients with a diagnosis of CRS who underwent sinus surgery in the department of otolaryngology at the Medical College of Georgia, Augusta. The researchers subdivided patients based on the presence or absence of an asthma diagnosis and further subdivided them based on tissue eosinophilia and nasal polyposis. Next, they compared the Sinonasal Outcome Test (SNOT-22), Lund-Kennedy endoscopy scores, and Lund-McKay CT scores preoperatively and postoperatively at 6 months – 1 year and at 2, 3, 4, and 5 years. They performed a T-test analysis to determine statistical significance.

Of the 457 patients included in the analysis, 92 had asthma and eosinophilic CRS with nasal polyps (eCRScNP), 20 had asthma and eosinophilic CRS without nasal polyps (eCRSsNP), 8 had asthma and noneosinophilic CRS with nasal polyps (neCRScNP), and 16 had asthma and noneosinophilic CRS without nasal polyps (neCRSsNP). The researchers observed that patients in the eCRScNP group showed no difference in QOL preoperatively, but their QOL declined significantly at the 1- and 2-year analysis (P less than .03). No significant QOL improvement appeared in the eCRSsNP group until 4 years (P less than .008), and there was no significant QOL difference among the neCRS groups regardless of nasal polyposis. A statistical difference in endoscopy scores was seen among patients in the preoperative neCRScNP group (P less than .001) and in the eCRScNP group from preoperatively until 5 years postoperatively (P less than .03). Finally, statistical significance appeared in preoperative CT scores analysis among patients in the eCRScNP group (P less than .001).

Dragana991/Getty Images

dbrunk@mdedge.com

CORONADO, CALIF. – Eosinophilic chronic rhinosinusitis with nasal polyposis decreases quality of life improvement after sinus surgery in patients with concurrent asthma, results from a retrospective study demonstrated.

They also have significantly higher Lund-Kennedy endoscopy and Lund-McKay CT scores, compared with control groups.

“Patients with concurrent asthma and chronic sinusitis require more aggressive management than nonasthmatics,” one of the study authors, Aykut A. Unsal, DO, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “Additionally, the degree of improvement of not only their sinusitis but possibly their asthma following medical/surgical treatment will also be limited if that patient also suffers from nasal polyps and/or eosinophilia. These patients will ultimately become more difficult to manage.”

In order to examine the relationship of eosinophilia and nasal polyps on quality of life (QOL) in patients with asthma who have chronic rhinosinusitis (CRS) who were treated with surgery, Dr. Unsal and his associates reviewed the records of 457 patients with a diagnosis of CRS who underwent sinus surgery in the department of otolaryngology at the Medical College of Georgia, Augusta. The researchers subdivided patients based on the presence or absence of an asthma diagnosis and further subdivided them based on tissue eosinophilia and nasal polyposis. Next, they compared the Sinonasal Outcome Test (SNOT-22), Lund-Kennedy endoscopy scores, and Lund-McKay CT scores preoperatively and postoperatively at 6 months – 1 year and at 2, 3, 4, and 5 years. They performed a T-test analysis to determine statistical significance.

Of the 457 patients included in the analysis, 92 had asthma and eosinophilic CRS with nasal polyps (eCRScNP), 20 had asthma and eosinophilic CRS without nasal polyps (eCRSsNP), 8 had asthma and noneosinophilic CRS with nasal polyps (neCRScNP), and 16 had asthma and noneosinophilic CRS without nasal polyps (neCRSsNP). The researchers observed that patients in the eCRScNP group showed no difference in QOL preoperatively, but their QOL declined significantly at the 1- and 2-year analysis (P less than .03). No significant QOL improvement appeared in the eCRSsNP group until 4 years (P less than .008), and there was no significant QOL difference among the neCRS groups regardless of nasal polyposis. A statistical difference in endoscopy scores was seen among patients in the preoperative neCRScNP group (P less than .001) and in the eCRScNP group from preoperatively until 5 years postoperatively (P less than .03). Finally, statistical significance appeared in preoperative CT scores analysis among patients in the eCRScNP group (P less than .001).

Dragana991/Getty Images

dbrunk@mdedge.com

CORONADO, CALIF. – Eosinophilic chronic rhinosinusitis with nasal polyposis decreases quality of life improvement after sinus surgery in patients with concurrent asthma, results from a retrospective study demonstrated.

They also have significantly higher Lund-Kennedy endoscopy and Lund-McKay CT scores, compared with control groups.

“Patients with concurrent asthma and chronic sinusitis require more aggressive management than nonasthmatics,” one of the study authors, Aykut A. Unsal, DO, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “Additionally, the degree of improvement of not only their sinusitis but possibly their asthma following medical/surgical treatment will also be limited if that patient also suffers from nasal polyps and/or eosinophilia. These patients will ultimately become more difficult to manage.”

In order to examine the relationship of eosinophilia and nasal polyps on quality of life (QOL) in patients with asthma who have chronic rhinosinusitis (CRS) who were treated with surgery, Dr. Unsal and his associates reviewed the records of 457 patients with a diagnosis of CRS who underwent sinus surgery in the department of otolaryngology at the Medical College of Georgia, Augusta. The researchers subdivided patients based on the presence or absence of an asthma diagnosis and further subdivided them based on tissue eosinophilia and nasal polyposis. Next, they compared the Sinonasal Outcome Test (SNOT-22), Lund-Kennedy endoscopy scores, and Lund-McKay CT scores preoperatively and postoperatively at 6 months – 1 year and at 2, 3, 4, and 5 years. They performed a T-test analysis to determine statistical significance.

Of the 457 patients included in the analysis, 92 had asthma and eosinophilic CRS with nasal polyps (eCRScNP), 20 had asthma and eosinophilic CRS without nasal polyps (eCRSsNP), 8 had asthma and noneosinophilic CRS with nasal polyps (neCRScNP), and 16 had asthma and noneosinophilic CRS without nasal polyps (neCRSsNP). The researchers observed that patients in the eCRScNP group showed no difference in QOL preoperatively, but their QOL declined significantly at the 1- and 2-year analysis (P less than .03). No significant QOL improvement appeared in the eCRSsNP group until 4 years (P less than .008), and there was no significant QOL difference among the neCRS groups regardless of nasal polyposis. A statistical difference in endoscopy scores was seen among patients in the preoperative neCRScNP group (P less than .001) and in the eCRScNP group from preoperatively until 5 years postoperatively (P less than .03). Finally, statistical significance appeared in preoperative CT scores analysis among patients in the eCRScNP group (P less than .001).

Dragana991/Getty Images

dbrunk@mdedge.com

Benralizumab is safe and effective for the treatment of uncontrolled asthma out to 2 years, according findings of the BORA trial, an extension study of the phase 3 SIROCCO and CALIMA trials. The study follows up and reinforces previously reported 1-year data and was reported by William W. Busse, MD, of University of Wisconsin, Madison, and his colleagues in the Lancet Respiratory Medicine.

Courtesy University of Wisconsin Health System

Benralizumab is a monoclonal antibody that targets interleukin-5 receptor alpha. It causes rapid deletion of eosinophils through cell-mediated cytotoxicity. A 30-mg dose of benralizumab every 8 weeks is approved for severe asthma treatment in Canada, Europe, Japan, the United States, and other countries.

In the second year of treatment, there were no new adverse events associated with depleted eosinophils, and the frequency of opportunistic infections was similar to that observed in the first year.

Eosinophilic inflammation occurs in about half of asthma cases and is associated with greater severity.

The 48-week SIROCCO trial, the 56-week CALIMA trial, and the 28-week ZONDA trial tested the effect of benralizumab 30 mg given every 4 weeks or 8 weeks, combined with high-dosage inhaled steroids and long-acting beta₂-agonists. The 8-week dose of the drug reduced annual exacerbations by 51%, compared with placebo in the SIROCCO trial and by 28% in the CALIMA trial. In the ZONDA trial, benralizumab reduced oral glucocorticoid use by 75%, compared with placebo, and by 25% from baseline.

The BORA extension trial included participants in the previous three trials. In the current report, researchers presented results from the analysis from BORA participants recruited from the SIROCCO and CALIMA trials. Data from participants from all three trials will be reported in the future.

The analysis included 1,576 patients who continued to receive benralizumab after being assigned to the treatment arm in SIROCCO or CALIMA, or who had received placebo were randomized to benralizumab on the 4-week (n = 783; 265 from placebo) or 8-week dose (n = 793; 281 from placebo) schedule.

A total of 166 patients, or about 10% in each group, discontinued treatment. The frequency of any serious adverse event (SAE) ranged between 10% and 11% in all groups. SAEs associated with infections ranged from 1% to 3%, indicating that there were no significant differences in SAE frequencies between those who were originally assigned to placebo and those who originally received benralizumab. That suggests no safety differences between receiving the drug for 1 year or 2 years.

A total of 1,046 subjects had blood eosinophil counts of 300 cells per mcL or greater at baseline; 72% of these patients had no asthma exacerbations during the BORA study. This was true for 74% of patients in the 8-week treatment arm.

The crude asthma exacerbation rate for patients who received benralizumab in SIROCCO or CALIMA was 0.48 in the 4-week arm, compared with placebo (95% confidence interval, 0.42-0.56) and 0.46 in the 8-week arm (95% CI, 0.39-0.53). For patients who started out on placebo, the crude exacerbation rate during BORA was 0.53 in the 4-week group (95% CI, 0.43-0.65) and 0.57 in the 8-week group (95% CI, 0.47-0.68).

Patients who started on benralizumab had similar exacerbation frequencies during year 1 and year 2.

AstraZeneca and Kyowa Hakko Kirin funded the studies. The authors have received fees from AstraZeneca and other pharmaceutical companies, and some are employees of AstraZeneca.

SOURCE: Busse WW et al. Lancet Respir Med. 2019 Jan 1;7(1):46-59.

Benralizumab is safe and effective for the treatment of uncontrolled asthma out to 2 years, according findings of the BORA trial, an extension study of the phase 3 SIROCCO and CALIMA trials. The study follows up and reinforces previously reported 1-year data and was reported by William W. Busse, MD, of University of Wisconsin, Madison, and his colleagues in the Lancet Respiratory Medicine.

Courtesy University of Wisconsin Health System

Benralizumab is a monoclonal antibody that targets interleukin-5 receptor alpha. It causes rapid deletion of eosinophils through cell-mediated cytotoxicity. A 30-mg dose of benralizumab every 8 weeks is approved for severe asthma treatment in Canada, Europe, Japan, the United States, and other countries.

In the second year of treatment, there were no new adverse events associated with depleted eosinophils, and the frequency of opportunistic infections was similar to that observed in the first year.

Eosinophilic inflammation occurs in about half of asthma cases and is associated with greater severity.

The 48-week SIROCCO trial, the 56-week CALIMA trial, and the 28-week ZONDA trial tested the effect of benralizumab 30 mg given every 4 weeks or 8 weeks, combined with high-dosage inhaled steroids and long-acting beta₂-agonists. The 8-week dose of the drug reduced annual exacerbations by 51%, compared with placebo in the SIROCCO trial and by 28% in the CALIMA trial. In the ZONDA trial, benralizumab reduced oral glucocorticoid use by 75%, compared with placebo, and by 25% from baseline.

The BORA extension trial included participants in the previous three trials. In the current report, researchers presented results from the analysis from BORA participants recruited from the SIROCCO and CALIMA trials. Data from participants from all three trials will be reported in the future.

The analysis included 1,576 patients who continued to receive benralizumab after being assigned to the treatment arm in SIROCCO or CALIMA, or who had received placebo were randomized to benralizumab on the 4-week (n = 783; 265 from placebo) or 8-week dose (n = 793; 281 from placebo) schedule.

A total of 166 patients, or about 10% in each group, discontinued treatment. The frequency of any serious adverse event (SAE) ranged between 10% and 11% in all groups. SAEs associated with infections ranged from 1% to 3%, indicating that there were no significant differences in SAE frequencies between those who were originally assigned to placebo and those who originally received benralizumab. That suggests no safety differences between receiving the drug for 1 year or 2 years.

A total of 1,046 subjects had blood eosinophil counts of 300 cells per mcL or greater at baseline; 72% of these patients had no asthma exacerbations during the BORA study. This was true for 74% of patients in the 8-week treatment arm.

The crude asthma exacerbation rate for patients who received benralizumab in SIROCCO or CALIMA was 0.48 in the 4-week arm, compared with placebo (95% confidence interval, 0.42-0.56) and 0.46 in the 8-week arm (95% CI, 0.39-0.53). For patients who started out on placebo, the crude exacerbation rate during BORA was 0.53 in the 4-week group (95% CI, 0.43-0.65) and 0.57 in the 8-week group (95% CI, 0.47-0.68).

Patients who started on benralizumab had similar exacerbation frequencies during year 1 and year 2.

AstraZeneca and Kyowa Hakko Kirin funded the studies. The authors have received fees from AstraZeneca and other pharmaceutical companies, and some are employees of AstraZeneca.

SOURCE: Busse WW et al. Lancet Respir Med. 2019 Jan 1;7(1):46-59.

Benralizumab is safe and effective for the treatment of uncontrolled asthma out to 2 years, according findings of the BORA trial, an extension study of the phase 3 SIROCCO and CALIMA trials. The study follows up and reinforces previously reported 1-year data and was reported by William W. Busse, MD, of University of Wisconsin, Madison, and his colleagues in the Lancet Respiratory Medicine.

Courtesy University of Wisconsin Health System

Benralizumab is a monoclonal antibody that targets interleukin-5 receptor alpha. It causes rapid deletion of eosinophils through cell-mediated cytotoxicity. A 30-mg dose of benralizumab every 8 weeks is approved for severe asthma treatment in Canada, Europe, Japan, the United States, and other countries.

In the second year of treatment, there were no new adverse events associated with depleted eosinophils, and the frequency of opportunistic infections was similar to that observed in the first year.

Eosinophilic inflammation occurs in about half of asthma cases and is associated with greater severity.

The 48-week SIROCCO trial, the 56-week CALIMA trial, and the 28-week ZONDA trial tested the effect of benralizumab 30 mg given every 4 weeks or 8 weeks, combined with high-dosage inhaled steroids and long-acting beta₂-agonists. The 8-week dose of the drug reduced annual exacerbations by 51%, compared with placebo in the SIROCCO trial and by 28% in the CALIMA trial. In the ZONDA trial, benralizumab reduced oral glucocorticoid use by 75%, compared with placebo, and by 25% from baseline.

The BORA extension trial included participants in the previous three trials. In the current report, researchers presented results from the analysis from BORA participants recruited from the SIROCCO and CALIMA trials. Data from participants from all three trials will be reported in the future.

The analysis included 1,576 patients who continued to receive benralizumab after being assigned to the treatment arm in SIROCCO or CALIMA, or who had received placebo were randomized to benralizumab on the 4-week (n = 783; 265 from placebo) or 8-week dose (n = 793; 281 from placebo) schedule.

A total of 166 patients, or about 10% in each group, discontinued treatment. The frequency of any serious adverse event (SAE) ranged between 10% and 11% in all groups. SAEs associated with infections ranged from 1% to 3%, indicating that there were no significant differences in SAE frequencies between those who were originally assigned to placebo and those who originally received benralizumab. That suggests no safety differences between receiving the drug for 1 year or 2 years.

A total of 1,046 subjects had blood eosinophil counts of 300 cells per mcL or greater at baseline; 72% of these patients had no asthma exacerbations during the BORA study. This was true for 74% of patients in the 8-week treatment arm.

The crude asthma exacerbation rate for patients who received benralizumab in SIROCCO or CALIMA was 0.48 in the 4-week arm, compared with placebo (95% confidence interval, 0.42-0.56) and 0.46 in the 8-week arm (95% CI, 0.39-0.53). For patients who started out on placebo, the crude exacerbation rate during BORA was 0.53 in the 4-week group (95% CI, 0.43-0.65) and 0.57 in the 8-week group (95% CI, 0.47-0.68).

Patients who started on benralizumab had similar exacerbation frequencies during year 1 and year 2.

AstraZeneca and Kyowa Hakko Kirin funded the studies. The authors have received fees from AstraZeneca and other pharmaceutical companies, and some are employees of AstraZeneca.

SOURCE: Busse WW et al. Lancet Respir Med. 2019 Jan 1;7(1):46-59.

Just like exposure to secondhand smoke, exposure to secondhand aerosols from e-cigarettes is associated with an increased risk of asthma exacerbations in children, according to a review of the 11,830 kids with asthma in the 2016 Florida Youth Tobacco survey.

diego_cervo/Thinkstock

Every year, the Florida Department of Health surveys public school children aged 11-17 years about various tobacco issues. In 2016, almost 12% of the asthmatic children in the survey said they vaped. Almost half were exposed to secondhand smoke, and a third reported exposure to secondhand vaping aerosols within the past 30 days. Overall, 21% reported an asthma attack in the past 12 months.

Using data from the Florida survey, the investigators crunched the numbers and found that secondhand aerosol exposure increased the odds of an asthma attack by 27%, independent of exposure to secondhand smoke and whether children smoked or vaped themselves (adjusted odds ratio, 1.27; 95% confidence interval, 1.11-1.47).

“Health professionals may wish to counsel asthmatic youth and their families regarding the potential risks of ENDS [electronic nicotine delivery system] use and exposure to ENDS aerosols.” Providers “may also consider including ENDS aerosol exposure as a possible trigger in asthma self-management/action plans and updating asthma home environment assessments to include exposure to ENDS aerosols,” said investigators led by medical student Jennifer Bayly, a research fellow at the National Institute on Minority Health and Health Disparities in Bethesda, Md.

About 4% of adults in the United States and 11% of high school students vape, and almost 10% of U.S. adolescents reported living with an ENDS user in 2014. Given the data, “it is likely that a substantial number of asthmatic youth are exposed,” the investigators said.

The study adds to a growing body of evidence linking e-cigarettes to asthma. There’s moderate evidence for increased cough and wheezing in adolescents who use e-cigarettes, plus an association with e-cigarette use and increased asthma exacerbations. The new study, however, is likely the first to look specifically at secondhand exposure among asthmatic children. Ingredients in vaping aerosols, including flavorings, propylene glycol, and vegetable glycerin, are physiologically active in the lungs, and may be lung irritants.

Overall, about half of the respondents were female, and two-thirds were 11-13 years old. About a third identified as Hispanic, a third as white, and just over a fifth as black. Three-quarters of the sample lived in large or midsized metropolitan areas, and close to two-thirds in stand-alone homes. Participants were considered exposed to secondhand aerosols if they reported that in the past month they were in a room or car with someone who was vaping.

The work was funded by the National Institutes of Health. The investigators had no disclosures.

aotto@mdedge.com

SOURCE: Bayly JE et al. CHEST®. 2018 Oct 22. doi: 10.1016/j.chest.2018.10.005.

Just like exposure to secondhand smoke, exposure to secondhand aerosols from e-cigarettes is associated with an increased risk of asthma exacerbations in children, according to a review of the 11,830 kids with asthma in the 2016 Florida Youth Tobacco survey.

diego_cervo/Thinkstock

Every year, the Florida Department of Health surveys public school children aged 11-17 years about various tobacco issues. In 2016, almost 12% of the asthmatic children in the survey said they vaped. Almost half were exposed to secondhand smoke, and a third reported exposure to secondhand vaping aerosols within the past 30 days. Overall, 21% reported an asthma attack in the past 12 months.

Using data from the Florida survey, the investigators crunched the numbers and found that secondhand aerosol exposure increased the odds of an asthma attack by 27%, independent of exposure to secondhand smoke and whether children smoked or vaped themselves (adjusted odds ratio, 1.27; 95% confidence interval, 1.11-1.47).

“Health professionals may wish to counsel asthmatic youth and their families regarding the potential risks of ENDS [electronic nicotine delivery system] use and exposure to ENDS aerosols.” Providers “may also consider including ENDS aerosol exposure as a possible trigger in asthma self-management/action plans and updating asthma home environment assessments to include exposure to ENDS aerosols,” said investigators led by medical student Jennifer Bayly, a research fellow at the National Institute on Minority Health and Health Disparities in Bethesda, Md.

About 4% of adults in the United States and 11% of high school students vape, and almost 10% of U.S. adolescents reported living with an ENDS user in 2014. Given the data, “it is likely that a substantial number of asthmatic youth are exposed,” the investigators said.

The study adds to a growing body of evidence linking e-cigarettes to asthma. There’s moderate evidence for increased cough and wheezing in adolescents who use e-cigarettes, plus an association with e-cigarette use and increased asthma exacerbations. The new study, however, is likely the first to look specifically at secondhand exposure among asthmatic children. Ingredients in vaping aerosols, including flavorings, propylene glycol, and vegetable glycerin, are physiologically active in the lungs, and may be lung irritants.

Overall, about half of the respondents were female, and two-thirds were 11-13 years old. About a third identified as Hispanic, a third as white, and just over a fifth as black. Three-quarters of the sample lived in large or midsized metropolitan areas, and close to two-thirds in stand-alone homes. Participants were considered exposed to secondhand aerosols if they reported that in the past month they were in a room or car with someone who was vaping.

The work was funded by the National Institutes of Health. The investigators had no disclosures.

aotto@mdedge.com

SOURCE: Bayly JE et al. CHEST®. 2018 Oct 22. doi: 10.1016/j.chest.2018.10.005.

Just like exposure to secondhand smoke, exposure to secondhand aerosols from e-cigarettes is associated with an increased risk of asthma exacerbations in children, according to a review of the 11,830 kids with asthma in the 2016 Florida Youth Tobacco survey.

diego_cervo/Thinkstock

Every year, the Florida Department of Health surveys public school children aged 11-17 years about various tobacco issues. In 2016, almost 12% of the asthmatic children in the survey said they vaped. Almost half were exposed to secondhand smoke, and a third reported exposure to secondhand vaping aerosols within the past 30 days. Overall, 21% reported an asthma attack in the past 12 months.

Using data from the Florida survey, the investigators crunched the numbers and found that secondhand aerosol exposure increased the odds of an asthma attack by 27%, independent of exposure to secondhand smoke and whether children smoked or vaped themselves (adjusted odds ratio, 1.27; 95% confidence interval, 1.11-1.47).

“Health professionals may wish to counsel asthmatic youth and their families regarding the potential risks of ENDS [electronic nicotine delivery system] use and exposure to ENDS aerosols.” Providers “may also consider including ENDS aerosol exposure as a possible trigger in asthma self-management/action plans and updating asthma home environment assessments to include exposure to ENDS aerosols,” said investigators led by medical student Jennifer Bayly, a research fellow at the National Institute on Minority Health and Health Disparities in Bethesda, Md.

About 4% of adults in the United States and 11% of high school students vape, and almost 10% of U.S. adolescents reported living with an ENDS user in 2014. Given the data, “it is likely that a substantial number of asthmatic youth are exposed,” the investigators said.

The study adds to a growing body of evidence linking e-cigarettes to asthma. There’s moderate evidence for increased cough and wheezing in adolescents who use e-cigarettes, plus an association with e-cigarette use and increased asthma exacerbations. The new study, however, is likely the first to look specifically at secondhand exposure among asthmatic children. Ingredients in vaping aerosols, including flavorings, propylene glycol, and vegetable glycerin, are physiologically active in the lungs, and may be lung irritants.

Overall, about half of the respondents were female, and two-thirds were 11-13 years old. About a third identified as Hispanic, a third as white, and just over a fifth as black. Three-quarters of the sample lived in large or midsized metropolitan areas, and close to two-thirds in stand-alone homes. Participants were considered exposed to secondhand aerosols if they reported that in the past month they were in a room or car with someone who was vaping.

The work was funded by the National Institutes of Health. The investigators had no disclosures.

aotto@mdedge.com

SOURCE: Bayly JE et al. CHEST®. 2018 Oct 22. doi: 10.1016/j.chest.2018.10.005.

ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.

That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.

Severe asthma challenges

These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.

Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.

xavier gallego morel/fotolia.com

The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta₂-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.

It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
 

Biologics for pediatric asthma

Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.

The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.

Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.

For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV₁) and overall quality of life.

Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV₁ or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).

Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.

Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.

Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV₁. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.

Dupilumab: New kid on the block

The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.

The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.

“It could be potentially better than those currently available due to additional effect on FEV₁,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.

As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.

“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”

Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.

ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.

That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.

Severe asthma challenges

These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.

Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.

xavier gallego morel/fotolia.com

The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta₂-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.

It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
 

Biologics for pediatric asthma

Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.

The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.

Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.

For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV₁) and overall quality of life.

Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV₁ or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).

Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.

Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.

Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV₁. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.

Dupilumab: New kid on the block

The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.

The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.

“It could be potentially better than those currently available due to additional effect on FEV₁,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.

As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.

“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”

Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.

ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.

That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.

Severe asthma challenges

These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.

Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.

xavier gallego morel/fotolia.com

The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta₂-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.

It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
 

Biologics for pediatric asthma

Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.

The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.

Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.

For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV₁) and overall quality of life.

Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV₁ or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).

Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.

Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.

Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV₁. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.

Dupilumab: New kid on the block

The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.

The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.

“It could be potentially better than those currently available due to additional effect on FEV₁,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.

As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.

“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”

Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Vitamin D levels measured in maternal sera during gestation and in umbilical cord blood were not predictive of the prevalence of eczema, food allergy, asthma and allergic rhinitis in children at ages 2 years and 5 years, according to study results published in the journal Allergy.

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Áine Hennessy, PhD, from the School of Food and Nutritional Sciences at the University College Cork (Ireland), and her colleagues performed a prospective cohort study of 1,537 women in the Cork BASELINE Birth Cohort Study who underwent measurement of serum 25-hydroxyvitamin D (25[OH]D) from maternal sera followed by measurement of 25(OH)D in umbilical cord blood (1,050 cases). They then measured the prevalence of eczema, food allergy, allergic rhinitis, and asthma in infants at aged 2 and 5 years.

The researchers found at 2 years old, 5% of infants had persistent eczema, 4% of infants had a food allergy and 8% of infants had aeroallergen sensitization. At age 5 years, 15% of infants had asthma, while 5% had allergic rhinitis. Mothers whose children went on to have atopy did not differ in their 25(OH)D levels at 15 weeks’ gestation (mean 58.4 nmol/L vs. 58.5 nmol/L) or in the levels in umbilical cord blood (mean 35.2 nmol/L and 35.4 nmol/L).

Of the women in the cohort, 74% ranged in age from 25 to 34 years; 49% reported a personal history of allergy and 37% reported a paternal allergy. The mean birth weight of the infants was 3,458 g; infants were breastfed for mean 11.9 weeks, 73% of infants were breastfeeding by the time they left the hospital and 45% of infants were breastfeeding by age 2 months.

Limitations of the study included that parental atopy status was self-reported and that the researchers noted they did not examine genetic variants of immunoglobulin E synthesis or vitamin D receptor polymorphisms.

“To fully characterize relationships between intrauterine vitamin D exposure and allergic disease, analysis of well‐constructed, large‐scale prospective cohorts of maternal‐infant dyads, which take due consideration of an individual’s inherited risk, early‐life exposures and environmental confounders, is still needed,” Dr. Hennessy and her colleagues wrote.

The study was funded by grants from the European Commission, Ireland Health Research Board, National Children’s Research Centre, Food Standards Agency and Science Foundation Ireland. The authors report no relevant conflicts of interest.

SOURCE: Hennessy A et al. Allergy. 2018 Aug 7. doi: 10.1111/all.13590.

Vitamin D levels measured in maternal sera during gestation and in umbilical cord blood were not predictive of the prevalence of eczema, food allergy, asthma and allergic rhinitis in children at ages 2 years and 5 years, according to study results published in the journal Allergy.

copyright istock/Thinkstock

Áine Hennessy, PhD, from the School of Food and Nutritional Sciences at the University College Cork (Ireland), and her colleagues performed a prospective cohort study of 1,537 women in the Cork BASELINE Birth Cohort Study who underwent measurement of serum 25-hydroxyvitamin D (25[OH]D) from maternal sera followed by measurement of 25(OH)D in umbilical cord blood (1,050 cases). They then measured the prevalence of eczema, food allergy, allergic rhinitis, and asthma in infants at aged 2 and 5 years.

The researchers found at 2 years old, 5% of infants had persistent eczema, 4% of infants had a food allergy and 8% of infants had aeroallergen sensitization. At age 5 years, 15% of infants had asthma, while 5% had allergic rhinitis. Mothers whose children went on to have atopy did not differ in their 25(OH)D levels at 15 weeks’ gestation (mean 58.4 nmol/L vs. 58.5 nmol/L) or in the levels in umbilical cord blood (mean 35.2 nmol/L and 35.4 nmol/L).

Of the women in the cohort, 74% ranged in age from 25 to 34 years; 49% reported a personal history of allergy and 37% reported a paternal allergy. The mean birth weight of the infants was 3,458 g; infants were breastfed for mean 11.9 weeks, 73% of infants were breastfeeding by the time they left the hospital and 45% of infants were breastfeeding by age 2 months.

Limitations of the study included that parental atopy status was self-reported and that the researchers noted they did not examine genetic variants of immunoglobulin E synthesis or vitamin D receptor polymorphisms.

“To fully characterize relationships between intrauterine vitamin D exposure and allergic disease, analysis of well‐constructed, large‐scale prospective cohorts of maternal‐infant dyads, which take due consideration of an individual’s inherited risk, early‐life exposures and environmental confounders, is still needed,” Dr. Hennessy and her colleagues wrote.

The study was funded by grants from the European Commission, Ireland Health Research Board, National Children’s Research Centre, Food Standards Agency and Science Foundation Ireland. The authors report no relevant conflicts of interest.

SOURCE: Hennessy A et al. Allergy. 2018 Aug 7. doi: 10.1111/all.13590.

Vitamin D levels measured in maternal sera during gestation and in umbilical cord blood were not predictive of the prevalence of eczema, food allergy, asthma and allergic rhinitis in children at ages 2 years and 5 years, according to study results published in the journal Allergy.

copyright istock/Thinkstock

Áine Hennessy, PhD, from the School of Food and Nutritional Sciences at the University College Cork (Ireland), and her colleagues performed a prospective cohort study of 1,537 women in the Cork BASELINE Birth Cohort Study who underwent measurement of serum 25-hydroxyvitamin D (25[OH]D) from maternal sera followed by measurement of 25(OH)D in umbilical cord blood (1,050 cases). They then measured the prevalence of eczema, food allergy, allergic rhinitis, and asthma in infants at aged 2 and 5 years.

The researchers found at 2 years old, 5% of infants had persistent eczema, 4% of infants had a food allergy and 8% of infants had aeroallergen sensitization. At age 5 years, 15% of infants had asthma, while 5% had allergic rhinitis. Mothers whose children went on to have atopy did not differ in their 25(OH)D levels at 15 weeks’ gestation (mean 58.4 nmol/L vs. 58.5 nmol/L) or in the levels in umbilical cord blood (mean 35.2 nmol/L and 35.4 nmol/L).

Of the women in the cohort, 74% ranged in age from 25 to 34 years; 49% reported a personal history of allergy and 37% reported a paternal allergy. The mean birth weight of the infants was 3,458 g; infants were breastfed for mean 11.9 weeks, 73% of infants were breastfeeding by the time they left the hospital and 45% of infants were breastfeeding by age 2 months.

Limitations of the study included that parental atopy status was self-reported and that the researchers noted they did not examine genetic variants of immunoglobulin E synthesis or vitamin D receptor polymorphisms.

“To fully characterize relationships between intrauterine vitamin D exposure and allergic disease, analysis of well‐constructed, large‐scale prospective cohorts of maternal‐infant dyads, which take due consideration of an individual’s inherited risk, early‐life exposures and environmental confounders, is still needed,” Dr. Hennessy and her colleagues wrote.

The study was funded by grants from the European Commission, Ireland Health Research Board, National Children’s Research Centre, Food Standards Agency and Science Foundation Ireland. The authors report no relevant conflicts of interest.

SOURCE: Hennessy A et al. Allergy. 2018 Aug 7. doi: 10.1111/all.13590.