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Drug Treatment of Asthma

By

Victor E. Ortega

, MD, PhD, Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine;


Frank Genese

, DO, Wake Forest School of Medicine

Last full review/revision Jul 2019| Content last modified Jul 2019
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Major drug classes commonly used in the treatment of asthma and asthma exacerbations include

  • Bronchodilators (beta-2 agonists, anticholinergics)

  • Corticosteroids

  • Leukotriene modifiers

  • Mast cell stabilizers

  • Methylxanthines

  • Immunomodulators

Drugs in these classes (see table Drug Treatment of Chronic Asthma) are inhaled, taken orally, or injected subcutaneously or intravenously; inhaled drugs come in aerosolized and powdered forms. Use of aerosolized forms with a spacer or holding chamber facilitates deposition of the drug in the airways rather than the pharynx; patients are advised to wash and dry their spacers after each use to prevent bacterial contamination. In addition, use of aerosolized forms requires coordination between actuation of the inhaler (drug delivery) and inhalation; powdered forms reduce the need for coordination, because drug is delivered only when the patient fully inhales with a good effort.

Table
icon

Drug Treatment of Asthma*

Drug

Form

Dosage

Comments

Children

Adults

Short-acting beta-agonists

Albuterol

HFA: 90 mcg/puff

Same as adults

2 puffs every 4–6 hours as needed and 2 puffs 15–30 minutes before exercise

Albuterol is used mainly as a rescue drug.

It is not recommended for maintenance treatment.

Regular use indicates diminishing asthma control and need for additional drug.

MDI-DPI is as effective as nebulized therapy if patients can coordinate the inhalation maneuver using the spacer and holding chamber.

Nebulized albuterol can be mixed with other nebulizer solutions.

DPI: 90 mcg/puff

≥ 4 years: Same as adults

< 4 years: Not used

2 puffs every 4–6 hours as needed and 2 puffs 15–30 minutes before exercise

Nebulized solution: 5 mg/mL and 0.63, 1.25, and 2.5 mg/3 mL

< 5 years: 0.63–2.5 mg in 3 mL of saline every 4–6 hours as needed

≥ 5 years: 0.05 mg/kg in 3 mL saline every 4–6 hours as needed (minimum 1.25 mg, maximum 2.5 mg)

1.25–5 mg in 3 mL saline every 4–6 hours as needed

Levalbuterol

HFA: 45 mcg/puff

< 5 years: Not established

≥ 5 years: Same as adults

2 puffs every 4–6 hours as needed

Levalbuterol is the R-isomer of albuterol. 0.63 mg is equivalent to 1.25 mg racemic albuterol.

Levalbuterol may have fewer adverse effects.

Nebulized solution: 0.31, 0.63, and 1.25 mg/3 mL and 1.25 mg/0.5 mL

< 5 years: 0.31–1.25 mg in 3 mL every 4–6 hours as needed

5–11 years: 0.31–0.63 mg every 8 hours as needed (maximum 0.63 mg every 8 hours)

12 years: Same as adults

0.63–1.25 mg every 6–8 hours as needed

Long-acting beta-2 agonists (not to be used as monotherapy)

Arformoterol

Nebulized solution: 15 mcg/2 mL

Not established

15–25 mcg every 12 hours

Arformoterol is the R-isomer of formoterol.

Formoterol

Nebulized solution: 20 mcg/2 mL

Not established

20 mcg every 12 hours

DPI form is no longer available.

Salmeterol

HFA: 21 mcg/puff

12 years: Same as adults

2 puffs every 12 hours; when taken before exercise, should be taken 30–60 minutes before exercise

Duration of action is 12 hours.

One dose nightly is helpful for nocturnal asthma.

Salmeterol is not to be used for acute symptom relief in an exacerbation.

DPI: 50 mcg/puff

< 4 years: Not established

4 years: Same as adults

1 puff every 12 hours and 30 minutes before exercise

Ultra–long-acting beta-2 agonists (not to be used as monotherapy)

Indacaterol

DPI: 75 mcg/puff

Not established

1 puff once a day

Olodaterol

SMI: 2.5 mcg/puff

Not established

2 puffs once a day

Vilanterol

DPI: 25 mcg/puff

Not established

1 puff once a day

Vilanterol is available only in combination with fluticasone 100 mcg or 200 mcg.

Anticholinergics

Ipratropium

HFA: 17 mcg/puff

< 12 years: Not established

12 years: Same as adults

2 puffs every 6 hours as needed (maximum 12 puffs/day)

Ipratropium may be mixed in the same nebulizer as albuterol.

It should not be used as first-line therapy.

Regular use provides no clear benefit for long-term maintenance therapy but should be added for treatment of acute symptoms.

Nebulized solution: 500 mcg (0.02%, 2 mL)

< 12 years: Not established

12 years: Same as adults

500 mcg every 6–8 hours as needed

Tiotropium

SMI: 1.25 mcg/puff

< 6 years: Not established

6 years: Same as adults

2 puffs once a day (max 2 puffs/day)

Tiotropium is longer acting than ipratropium.

The lower dose SMI tiotropium is the only dose recommended for use in asthma.

DPI: 18 mcg/capsule

Not established

18 mcg (1 capsule) once a day

Corticosteroids (inhaled)

Beclomethasone

HFA: 40–80 mcg/puff

< 5 years: Not established

5–11 years: 1 puff every 12 hours (usual maximum 80 mcg twice a day)

12 years: Same as adults

1–2 puffs every 12 hours (usual maximum 320 mcg twice a day)

Doses depend on severity and range from 1–2 puffs to whatever dose is needed to control asthma.

All may have systemic effects when used long term.

Maximum threshold is that above which hypothalamic- pituitary-adrenal suppression is produced.

If higher doses are necessary for asthma control, specialist consultation is recommended.

Budesonide

DPI: 90 or 180 mcg/puff

< 6 years: Not recommended

6 years: Initial dose of 180 mcg twice a day (maximum 360 mcg twice a day)

Initial dose of 360 mcg twice a day (maximum 720 mcg twice a day)

Nebulized solution: 0.25, 0.5, or 1.0 mg (each in 2 mL solution)

1–8 years only: If previously taking bronchodilators alone, initial dose of 0.5 mg once a day or 0.25 mg twice a day (maximum 0.5 mg/day)

If previously taking inhaled corticosteroids, initial dose of 0.5 mg once a day or 0.25 mg twice a day

If previously taking oral corticosteroids, initial dose of 0.5 mg twice a day or 1 mg once a day (maximum 1 mg/day)

Not indicated for adults

Ciclesonide

HFA: 80 or 160 mcg/puff

≤ 5 years: 160 mcg daily

6–11 years: Low dose = 80 mcg once a day, medium dose > 80 to 160 mcg once a day, high dose > 160 mcg once a day

≥ 12 years: Same as adult

If previously taking bronchodilators alone, initial dose of 80 mcg twice a day (maximum 320 mcg twice a day)

If previously taking inhaled corticosteroids, initial dose of 80 mcg twice a day (maximum 640 mcg twice a day)

If previously taking oral corticosteroids, initial dose of 320 mcg twice a day (maximum 640 mcg twice a day)

Flunisolide

HFA: 80 mcg/puff

< 5 years: Not established

5–11 years: 1 puff twice a day (maximum 2 puffs twice a day [320 mcg/day])

12 years: Same as adults

2 puffs twice a day (maximum 4 puffs twice a day [640 mcg/day])

Fluticasone propionate

HFA: 44, 110, or 220 mcg/puffs

4–11 years: 88 mcg twice a day

12 years: Same as adults

If previously taking bronchodilators alone, initial dose of 88 mcg twice a day (maximum 440 mcg twice a day)

If previously taking inhaled corticosteroids, initial dose of 88–220 mcg twice a day (maximum 440 mcg twice a day)

If previously taking oral corticosteroids, initial dose of 440–880 mcg twice a day (maximum 880 mcg twice a day)

DPI: 50, 100, or 250 mcg/puff

0–4 years: not established

5–11 years: Initial dose of 50 mcg twice a day (maximum 100 mcg twice a day)

12 years: Same as adults

If previously taking bronchodilators alone, initial dose of 100 mcg twice a day (maximum 500 mcg twice a day)

If previously taking inhaled corticosteroids, initial dose of 100–250 mcg twice a day (maximum 500 mcg twice a day)

If previously taking oral corticosteroids, initial dose of 500–1000 mcg twice a day (maximum 1000 mcg twice a day)

Fluticasone furoate

DPI: 50, 100, or 200 mcg/puff

0–4 years: Not established

5–11 years: 1 puff (50 mcg) once a day

≥ 12 years: Same as adults

If previously taking bronchodilators alone, initial dose of 100 mcg once a day (maximum 200 mcg/day)

If previously taking inhaled corticosteroids, initial dose of 100-200 mcg once a day (maximum 200 mcg/day)

Mometasone

DPI: 110 or 220 mcg/puff

< 4 years: Not established

4–11 years: 110 mcg once a day in the evening

12 years: Same as adults

If previously taking bronchodilators alone or inhaled corticosteroids, initial dose of 220 mcg once a day in the evening (maximum 220 mcg twice a day or 440 mcg once a day in the evening)

If previously taking oral corticosteroids, initial dose of 440 mcg twice a day (maximum 880 mcg twice a day)

HFA: 100 or 200 mcg/puff

< 12 years: Not established

12 years: Same as adults

If previously taking bronchodilators alone, initial dose of 220 mcg (delivering 200 mcg) once or twice a day (maximum 440 mcg/day)

If previously taking inhaled corticosteroids, initial dose of 110–220 mcg (delivering 100 or 200 mcg) twice a day , (maximum 800 mcg/day)

If previously taking oral corticosteroids, initial dose of 440 mcg (delivering 400 mcg) twice a day (maximum 800 mcg/day)

Systemic corticosteroids (oral)

Methylprednisolone

Tablets: 2, 4, 8, 16, or 32 mg

0–11 years: Short-course burst: 1–2 mg/kg once a day (maximum 60 mg) for 3–10 days

12 years: Same as adults

7.5–60 mg once a day in the morning or every other day in the morning

Short-course burst: 40–60 mg once a day (or 20–30 mg twice a day) for 3–10 days

Maintenance doses should be given in a single dose in the morning every day or every other day as needed for control.

Some evidence suggests clinical effectiveness increases with no increase in adrenal suppression when dose is given at 3 PM.

Short-course burst doses are effective for establishing control when initiating therapy or during a period of gradual deterioration.

The burst should be continued until PEF = 80% of personal best or symptoms resolve, possibly requiring > 3–10 days of therapy.

Prednisolone

Tablets: 5 mg

Solution: 5 mg/5 mL or 15 mg/5 mL

Prednisone

Tablets: 1, 2.5, 5, 10, 20, or 50 mg

Solution: 5 mg/mL or 5 mg/5 mL

Combination drugs

Ipratroprium and albuterol

SMI: 20 mcg/puff ipratropium and 100 mcg/puff albuterol

Not established

1 puff qid (maximum 6 puffs/day)

Ipratroprium prolongs bronchodilator effect of albuterol.

Nebulized solution: 0.5 mg ipratropium and 2.5 mg albuterol in a 3-mL vial

3-mL vial via nebulization 4 times a day for ambulatory rescue therapy (maximum 6 doses/24 hours)

Fluticasone and salmeterol

DPI: 100, 250, or 500 mcg fluticasone and 50 mcg salmeterol

< 4 years: Not established

4–11 years: 1 puff (100/50) twice a day

12 years: Same as adults

1 puff twice a day

The 250/50 dose is indicated for asthma not controlled by low-to-medium doses of inhaled corticosteroids.

The 500/50 dose is indicated for asthma not controlled by medium-to-high doses of inhaled corticosteroids.

HFA: 45, 115, or 230 mcg fluticasone and 21 mcg salmeterol

< 12 years: Not established

12 years: Same as adults

2 puffs twice a day

Budesonide and formoterol

HFA: 80 or 160 mcg budesonide and 4.5 mcg formoterol

< 12 years: Not established

12 years: Same as adults

2 puffs twice a day (maximum 2 puffs of 160/4.5 mcg twice a day)

The 80/4.5 dose is indicated for asthma not controlled by low-to-medium doses of inhaled corticosteroids.

The 160/4.5 dose is indicated for asthma not controlled by medium-to-high doses of inhaled corticosteroids.

Mometasone and formoterol

HFA: 100 mcg or 200 mcg mometasone and 5 mcg formoterol

< 5 years: Not established

≥ 5 years: Same as adults

2 puffs twice a day

The 100/5 dose is recommended for asthma not controlled by low-to-medium–dose inhaled corticosteroids.

The 200/5 dose is recommended for asthma not controlled by high-dose inhaled corticosteroids.

Fluticasone and vilanterol

DPI: 100 or 200 mcg fluticasone and 25 mcg vilanterol

Not established

1 puff once/day

Recommended starting dose is based on asthma severity.

Mast cell stabilizers

Cromolyn

Nebulized solution: 20 mg/ampule

< 2 years: Not established

2 years: Same as adults

1 ampule 3 or 4 times a day

Cromolyn should be taken before exercise or allergen exposure.

One dose provides effective prophylaxis for 1–2 hours.

Leukotriene modifiers

Montelukast

Tablets, chewable tablets, and granules: 4, 5, or 10 mg

12 mo–5 years: 4 mg orally once a day in the evening

6–14 years: 5 mg orally once a day in the evening

15 years: Same as adults

10 mg orally once a day in the evening

Exercise-induced asthma: 10 mg orally 2 hours before exercise

Montelukast is a leukotriene receptor antagonist that is a competitive inhibitor of leukotrienes D4 and E4.

Zafirlukast

Tablet: 10 or 20 mg

< 5 years: Not established

5–11 years: 10 mg orally twice a day

12 years: Same as adults

20 mg orally in the evening

Zafirlukast is a leukotriene receptor antagonist that is a competitive inhibitor of leukotrienes D4 and E4.

It must be taken 1 hour before or 2 hours after meals.

Zileuton

Tablet, immediate-release: 600 mg

<12 years: Not established

12 years: Same as adults

600 mg orally 4 times a day

Zileuton inhibits 5-lipoxygenase.

Dosing may limit adherence.

Zileuton may cause liver enzyme elevations and inhibit metabolism of drugs processed by CYP3A4, including theophylline.

Extended-release: 1200 mg

< 12 years: Not established

≥ 12 years: Same as adults

1200 mg orally twice a day within 1 hour after morning and evening meals

Methylxanthines

Theophylline

Capsule, extended-release: 100, 200, 300, and 400 mg

Elixir: 80 mg/15 mL

Tablet, extended-release: 100, 200, 400, 450, or 600 mg

Initial dose of 10 mg/kg/day up to 600 mg/day, then adjusted to achieve a serum concentration of 5–15 mcg/mL at steady state

Initial dose of 10 mg/kg/day up to 600 mg/day, then adjusted to achieve a serum concentration of 5–15 mcg/mL at steady state

The wide variability in metabolic clearance, drug interactions, and potential for adverse effects mandate routine serum level monitoring.

Availability of safer alternatives has led to declining use of this drug.

Safety may be better with a target level < 10 mcg/mL.

Immunomodulators

Benralizumab

Subcutaneous injection: 30 mg/mL

< 12 years: Not established

>12 years: Same as adults

30 mg subcutaneously every 4 weeks for 3 doses then every 8 weeks thereafter

Benralizumab is used as an add-on treatment for patients with the eosinophilic phenotype.

Dupilumab

Subcutaneous injection: 300 mg/2mL or 200 mg/1.14 mL

< 12 years: Not established

≥ 12 years: Same as adults

400 mg subcutaneously once then 200 mg every 2 weeks or 600 mg subcutaneously once then 300 mg every 2 weeks

The initial dose should be given as two injections.

Dupilumab is used as an add-on treatment for patients with the eosinophilic phenotype.

Mepolizumab

Subcutaneous injection: 100 mg

< 12 years: Not established

≥ 12 years: Same as adults

100 mg subcutaneously once every 4 weeks

Omalizumab

Subcutaneous injection: 150 mg/1.2 mL

< 12 years: 75–375 mg subcutaneously every 2–4 weeks, depending on body weight and serum IgE level

≥ 12 years: Same as adults

150–375 mg subcutaneously every 2–4 weeks, depending on body weight and pretreatment serum IgE level

Maximum dose per injection site is 150 mg.

Reslizumab

Intravenous: 100 mg/10 mL

Not established

3 mg/kg IV once every 4 weeks

* All ages unless specified differently.

DPI = dry-powder inhaler; HFA = hydrofluoroalkane; MDI = metered-dose inhaler; SMI = soft mist inhaler; PEF = peak expiratory flow.

Adapted from the National Heart, Lung, and Blood Institute: Expert Panel Report 3, Guidelines for the diagnosis and management of asthma—full report 2007. August 28, 2007. Available at www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.

Beta-2 agonists

Beta-2 agonists relax bronchial smooth muscle, decrease mast cell degranulation and histamine release, inhibit microvascular leakage into the airways, and increase mucociliary clearance. Beta-2 agonist preparations may be short-acting, long-acting, or ultra–long-acting (see tables Drug Treatment of Chronic Asthma and Drug Treatment of Asthma Exacerbations).

Short-acting beta-2 agonists (eg, albuterol) 2 puffs every 4 hours inhaled as needed are the drug of choice for relieving acute bronchoconstriction and preventing exercise-induced asthma. They should not be used alone for long-term maintenance of chronic asthma. They take effect within minutes and are active for up to 6 to 8 hours, depending on the drug. Tachycardia and tremor are the most common acute adverse effects of inhaled beta-2 agonists and are dose-related. Mild hypokalemia occurs uncommonly. Use of levalbuterol (a solution containing the R-isomer of albuterol) theoretically minimizes adverse effects, but its long-term efficacy and safety are unproved. Oral beta-2 agonists have more systemic effects and generally should be avoided.

Long-acting beta-2 agonists (eg, salmeterol) are active for up to 12 hours. They are used for moderate and severe asthma but should never be used as monotherapy. They interact synergistically with inhaled corticosteroids and permit lower dosing of corticosteroids.

Ultra-long-acting beta-2 agonists (eg, indacaterol) are active for up to 24 hours and as with long-acting beta agonists are used for moderate to severe asthma, and should never be used as a monotherapy. They interact synergistically with inhaled corticosteroids and permit lower dosing of corticosteroids.

The safety of regular long-term use of beta-2 agonists remains unclear. Long-acting beta-2 agonists may increase the risk of asthma-related death when used as monotherapy. Therefore, when treating patients with asthma, these drugs (salmeterol, formoterol, vilanterol) should be used only in combination with an inhaled corticosteroid for patients whose condition is not adequately controlled with other asthma controllers (eg, low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants additional maintenance therapies. Daily use or diminishing effects of short-acting beta-2 agonists or use of ≥ 1 canister per month suggests inadequate control and the need to begin or intensify other therapies.

Anticholinergics

Anticholinergics relax bronchial smooth muscle through competitive inhibition of muscarinic (M3) cholinergic receptors. Ipratropium may have an additive effect when combined with short-acting beta-2 agonists. Adverse effects include pupillary dilation, blurred vision, and dry mouth. Tiotropium soft mist inhaler (1.25 mcg/puff) is a 24-hour inhaled anticholinergic that can be used for patients with asthma. In patients with asthma, clinical trials of tiotropium added to either inhaled corticosteroids or to a combination of an inhaled long-acting beta-2 agonist plus a corticosteroid have shown improved pulmonary function and decreased asthma exacerbations.

Corticosteroids

Corticosteroids inhibit airway inflammation, reverse beta-receptor down-regulation, and inhibit cytokine production and adhesion protein activation. They block the late response (but not the early response) to inhaled allergens. Routes of administration include oral, IV, and inhaled. In acute asthma exacerbations, early use of systemic corticosteroids often aborts the exacerbation, decreases the need for hospitalization, prevents relapse, and speeds recovery. Oral and IV routes are equally effective.

Inhaled corticosteroids have no role in acute exacerbations but are indicated for long-term suppression, control, and reversal of inflammation and symptoms. They substantially reduce the need for maintenance oral corticosteroid therapy. Adverse local effects of inhaled corticosteroids include dysphonia and oral candidiasis, which can be prevented or minimized by having the patient use a spacer, gargle with water after corticosteroid inhalation, or both. Systemic effects are all dose related, can occur with oral or inhaled forms, and occur mainly with inhaled doses > 800 mcg/day. They include suppression of the adrenal-pituitary axis, osteoporosis, cataracts, skin atrophy, hyperphagia, and easy bruisability. Whether inhaled corticosteroids suppress growth in children is unclear. Most children treated with inhaled corticosteroids eventually reach their predicted adult height. Latent tuberculosis may be reactivated by systemic corticosteroid use.

Mast cell stabilizers

Mast cell stabilizers inhibit histamine release from mast cells, reduce airway hyperresponsiveness, and block the early and late responses to allergens. They are given by inhalation prophylactically to patients with exercise-induced or allergen-induced asthma. They are ineffective once symptoms have occurred. They are the safest of all antiasthmatic drugs but the least effective.

Leukotriene modifiers

Leukotriene modifiers are taken orally and can be used for long-term control and prevention of symptoms in patients with mild persistent to severe persistent asthma. The main adverse effect is liver enzyme elevation (which occurs with zileuton). Although rare, patients have developed a clinical syndrome resembling eosinophilic granulomatosis with polyangiitis.

Methylxanthines

Methylxanthines relax bronchial smooth muscle (probably by inhibiting phosphodiesterase) and may improve myocardial and diaphragmatic contractility through unknown mechanisms. Methylxanthines appear to inhibit intracellular release of calcium, decrease microvascular leakage into the airway mucosa, and inhibit the late response to allergens. They decrease the infiltration of eosinophils into bronchial mucosa and of T cells into epithelium.

The methylxanthine theophylline is used for long-term control as an adjunct to beta-2 agonists. Extended-release theophylline helps manage nocturnal asthma. Theophylline has fallen into disuse because of its many adverse effects and interactions compared with other drugs. Adverse effects include headache, vomiting, cardiac arrhythmias, seizures, and aggravation of gastroesophageal reflux (by reducing lower esophageal sphincter pressure).

Methylxanthines have a narrow therapeutic index; multiple drugs (any metabolized by the cytochrome P-450 pathway, eg, macrolide antibiotics) and conditions (eg, fever, liver disease, heart failure) alter methylxanthine metabolism and elimination. Serum theophylline levels should be monitored periodically and maintained between 5 and 15 mcg/mL (28 and 83 micromole/L).

Immunomodulators

Immunomodulators include omalizumab, an anti-IgE antibody, 3 antibodies to IL-5 (benralizumab, mepolizumab, reslizumab), and a monoclonal antibody that inhibits IL-4 and IL-13 signaling (dupilumab), which are used for the management of severe allergic asthma.

Omalizumab is indicated for patients with severe, allergic asthma who have elevated IgE levels. Omalizumab may decrease asthma exacerbations, corticosteroid requirements, and symptoms. Dosing is determined by a dosing chart based on the patient’s weight and IgE levels. The drug is administered subcutaneously every 2 to 4 weeks.

Mepolizumab, reslizumab, and benralizumab were developed for use in patients with eosinophilic asthma and are monoclonal antibodies that block IL-5. IL-5 is a cytokine that promotes eosinophilic inflammation in the airways.

Mepolizumab reduces exacerbation frequency, decreases asthma symptoms, and reduces the need for systemic corticosteroid therapy in patients with asthma who are dependent on chronic systemic corticosteroid therapy. Based on data from clinical trials, efficacy occurs with blood absolute eosinophil counts > 150/microL (0.15 × 109/L); however, for patients on chronic systemic corticosteroid therapy, the threshold for efficacy is unclear. Mepolizumab is administered subcutaneously 100 mg every 4 weeks.

Reslizumab also appears to reduce frequency of exacerbations and decrease asthma symptoms. In clinical trials, patients had blood absolute eosinophil counts of about 400/microL (0.4 × 109/L). In patients treated with chronic systemic corticosteroids, the eosinophil count threshold for efficacy is unclear. Reslizumab is administered 3 mg/kg IV over 20 to 50 minutes every 4 weeks.

Benralizumab is a monoclonal antibody that binds to IL-5 receptors. It is indicated for the add-on maintenance treatment of severe asthma in patients aged 12 years or older with an eosinophilic phenotype. It has been shown to decrease exacerbation frequency and reduce and/or eliminate oral corticosteroid use. The recommended dose is 30 mg subcutaneously once every 4 weeks for 3 doses, followed by 30 mg once every 8 weeks. The treatment regimens of participants in clinical trials (1, 2references) included high-dose inhaled corticosteroids plus long-acting beta-2 agonists with or without other controllers. Blood eosinophil counts were typically > 300/microL (>0.3 × 109/L).

Dupilumab is a monoclonal antibody that blocks the IL-4R-alpha subunit, thereby simultaneously inhibiting IL-4 and IL-13 signaling. It is indicated for add-on maintenance treatment of patients with moderate-to-severe asthma aged 12 years or older with an eosinophilic phenotype or with oral corticosteroid–dependent asthma. The recommended dose is an initial dose of 400 mg subcutaneously followed by 200 mg every other week, or an initial dose of 600 mg subcutaneously followed by 300 mg every other week. The higher dosage is recommended for patients requiring concomitant oral corticosteroids or with co-morbid moderate-to-severe atopic dermatitis.

Clinicians who give any of these immunomodulators should be prepared to identify and treat anaphylaxis or allergic hypersensitivity reactions. Anaphylaxis may occur after any dose of dupilumab, benralizumab, omalizumab, or reslizumab even if previous doses have been well tolerated. Allergic hypersensitivity reactions have been reported with mepolizumab. Mepolizumab use has been associated with herpes zoster infection; therefore, zoster vaccination is recommend prior to initiation of therapy unless contraindicated.

Pearls & Pitfalls

  • Prepare for possible anaphylactic or hypersensitivity reactions in patients being treated with omalizumab, mepolizumab, reslizumab, benralizumab, or dupilumab regardless of how such treatments have been tolerated previously.

Other drugs

Other drugs are used in asthma treatment uncommonly and in specific circumstances. Magnesium is often used in the emergency department, but it is not recommended in the management of chronic asthma.

Immunotherapy may be indicated when symptoms are triggered by allergy, as suggested by history and confirmed by allergy testing. Immunotherapy is generally more effective in children than adults. If symptoms are not significantly relieved after 24 months, then therapy is stopped. If symptoms are relieved, therapy should continue for 3 years, although the optimum duration is unknown.

Other drugs that suppress the immune system are occasionally given to reduce dependence on high-dose oral corticosteroids, but these drugs have a significant risk of toxicity. Low-dose methotrexate (5 to 15 mg orally or IM once a week) can lead to modest improvements in FEV1 and modest decreases in daily oral corticosteroid use. Gold and cyclosporine are also modestly effective, but toxicity and need for monitoring limit their use.

Other therapies for management of chronic asthma include nebulized lidocaine, nebulized heparin, colchicine, and high-dose IV immune globulin. Limited evidence supports the use of any of these therapies, and their benefits are unproved, so none are currently recommended for routine clinical use.

References

  • 1. Bleecker ER, FitzGerald AM, Chanez P, et al: Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet388(10056):2115–2127, 2016. doi: 10.1016/S0140-6736(16)31324-1

  • 2. FitzGerald AM, Bleecker ER, Nair P, et al: Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 388(10056):2128–2141, 2016. doi: 10.1016/S0140-6736(16)31322-8

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