Table 1 Approved add-on asthma treatments

Anti-muscarinic

Tiotropium Respimat®, ≥ 6 years [31, 35,36,37,38]

2.5 µg (2 × 1.25 µg/puff) once daily (US FDA-approved dose) or 5 µg (2 × 2.5 µg/puff) once daily

• Improved peak FEV_1(0–3 h) and trough FEV₁

• Increased time to first severe exacerbation

Common AEs: nasopharyngitis, headache, bronchitis, and upper respiratory tract infection

Useful across all phenotypes of GINA Step 4/5 asthma and severe, uncontrolled asthma

Anti-IgE

Omalizumab, ≥ 6 years [50, 59,60,61,62,63]

75–375 mg SC Q2W or Q4W; (varies by serum total IgE level and weight)

• Reduced exacerbation rate, emergency visits, and rescue medication use

• Improved FEV₁, ACT, AQLQ, and IGETE scores

Common AEs: asthma, upper or lower respiratory tract infection, nasopharyngitis, sinusitis, bronchitis, and headache

Indicated in patients with positive skin test or in vitro reactivity to a perennial aeroallergen and serum total IgE levels: 30–700 IU/mL

Useful in patients with Th2-high phenotype

Anti-IL-5

Mepolizumab, ≥ 6 years [48, 70,71,72]

100 mg SC Q4W

• Reduced asthma exacerbation risk and blood eosinophil counts

• Improved FEV₁ and SGRQ and ACQ-5 scores

Common AEs: headache and nasopharyngitis

Useful in patients with baseline blood eosinophil counts ≥ 150 cells/µL

Reslizumab, ≥ 18 years [47, 73,74,75,76]

3 mg/kg Q4W IV infusion over 20–50 min

• Improved FEV₁, FVC, and FEF_25–75%, ACQ, and AQLQ scores

• Reduced frequency of asthma exacerbations and rescue medication use

Common AEs: worsening of asthma, headache, nasopharyngitis, upper respiratory tract infection, sinusitis, influenza, and headache

Useful in patients with baseline blood eosinophil counts ≥ 400 cells/µL

Benralizumab, ≥ 12 years [49, 80, 81]

30 mg Q4W SC for the first three doses, followed by Q8W thereafter

• Reduced annual asthma exacerbation rate, blood eosinophil counts, ACQ-6 scores, and corticosteroid dose

• Improved prebronchodilator FEV₁

Common AEs: worsening asthma, nasopharyngitis, and upper respiratory tract infection

Useful in patients with baseline blood eosinophil ≥ 300 cells/µL

Anti-IL-4Rα

Dupilumab, ≥ 12 years [51, 82]

Initial dose (600 or 400 mg), followed by 300 or 200 mg given every other week

• Reduced annual severe asthma exacerbations rate and oral glucocorticosteroid use

• Increased FEV₁

Transient eosinophilia observed

Useful in patients with moderate-to-severe asthma with baseline blood eosinophils ≥ 300 cells/µL or with oral corticosteroid-dependent asthma

Anti-TSLP

Tezepelumab, ≥ 12 years [53]

210 mg SC Q4W

• Reduced annual asthma exacerbations

• Reduced exacerbations, which required emergency room visits and/or hospitalization

• Improved FEV₁

Common AEs: pharyngitis, arthralgia, and back pain

Useful in patients with severe asthma irrespective of their phenotype (e.g., eosinophilic or allergic) or biomarker limitation