The latest GINA update includes these important add-on biologic therapy guidelines

The prevalence of asthma continues to grow in many countries—particularly among children. Despite the optimal use of inhaled corticosteroids (ICS) and long-acting β2-agonist (LABA) therapies, between 30% and 50% of patients with moderate-to-severe asthma have persistent symptoms and/or exacerbations, according to a study published in Respiratory Medicine.^[]

Every year, the Global Initiative for Asthma Strategy (GINA) publishes a strategy report to help establish up-to-date, evidence-based, clinical resources for physicians—the most recent was published in May 2024.^[] Launched in 1993 through a collaboration between the WHO and the US National Heart, Lung, and Blood Institute, GINA publishes an annual update to help clinicians sort through new evidence and approved therapies.

Recommendations

Approximately 3% to 10% of individuals with asthma have severe symptoms,^[] which is characterized as asthma that is “uncontrolled despite optimized treatment with high-dose ICS-LABA, or that requires high-dose ICS-LABA or biological therapy to prevent it from being uncontrolled.”^[]

In these patients, GINA guidelines recommend assessing the clinical and inflammatory phenotype, as this would be beneficial in selection of add-on maintenance treatment. 

Recommended add-on treatment options include adding tiotropium in a separate inhaler (patients ≥ 6 years of age), which provides modest improvement in lung function. Low-dose azithromycin may also reduce exacerbations, but use is limited to adults. 

Benefits of add-on biologics include substantial reductions in severe exacerbations and potential reduction in oral corticosteroid use. GINA recommends low-dose maintenance oral corticosteroids (OCS) as “a last resort if there are no other options available, because of their serious cumulative long-term side-effects.”^[]

Add-on treatment response should be assessed at follow-up, and ineffective therapies should be discontinued and/or adjusted. Patients who respond to add-on therapy should be re-evaluated every 3 months. Multidisciplinary care for patients with severe asthma is recommended to optimize patient outcomes.

Add-on biologic agents

Benralizumab

Benralizumab is an IL-5 receptor alpha-directed cytolytic monoclonal antibody indicated for the add-on maintenance treatment of patients with severe asthma with an eosinophilic phenotype who are aged ≥ 12 years.^[]

Administered by subcutaneous (SC) injection, the recommended dose is 30 mg every 4 weeks for 3 doses, and once every 8 weeks thereafter. Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria) have occurred. Adverse events (≥ 5%) include headache and pharyngitis.

Dupilumab

Dupilumab is an IL-4 receptor alpha antagonist indicated as an add-on maintenance treatment in patients aged 6 years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype or in those with oral corticosteroid-dependent asthma.^[]

The recommended dosage in patients ≥ 12 years is an initial loading dose of 400 mg or 600 mg SC, followed by 200 mg or 300 mg SC every 2 weeks, respectively. Dosing in patients 6 to 11 years of age is based on body weight: 300 mg every 4 weeks for 15 kg–30 kg; 200 mg SC every 2 weeks for ≥ 30 kg. 

Adverse reactions include injection site reactions, oropharyngeal pain, and eosinophilia. Hypersensitivity reactions have occurred.

Mepolizumab

Mepolizumab is an IL-5 antagonist monoclonal antibody indicated for add-on maintenance treatment in patients aged ≥ 6 years with severe asthma and with an eosinophilic phenotype.^[] The recommended dose in patients aged ≥ 12 years is 100 mg SC every 4 weeks; and 40 mg SC every 4 weeks in those aged 6 to 11 years. Common adverse events include headache, injection site reaction, back pain, and fatigue. Hypersensitivity reactions have occurred.

Reslizumab

Reslizumab is an IL-5 antagonist monoclonal antibody indicated for add-on maintenance treatment of patients with severe asthma aged ≥ 18 years and with an eosinophilic phenotype.^[] The recommended regimen is 3 mg/kg every 4 weeks by IV infusion over 20 to 50 minutes. Reslizumab may be associated with oropharyngeal pain.

Tezepelumab

Tezepelumab is a thymic stromal lymphopoietin blocker human monoclonal antibody indicated for the add-on treatment of patients aged ≥ 12 years with severe asthma.^[] The recommended dosage is 210 mg SC every 4 weeks. Adverse reactions may include pharyngitis, arthralgia and back pain; hypersensitivity reactions (eg, rash, allergic conjunctivitis) can occur. 

Omalizumab

Omalizumab is an anti-IgE antibody indicated for moderate-to-severe persistent asthma in patients aged 6 years and older with a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.^[]

Omalizumab may be dosed from 75 mg–375 mg SC every 2 to 4 weeks based on serum total IgE level and body weight (kg). 

Adverse events in patients 12 years of age and older may include arthralgia, pain (general), leg pain, fatigue, dizziness, fracture, arm pain, pruritus, dermatitis, and earache. Patients aged 6 to ≤ 12 years may see nasopharyngitis, headache, pyrexia, upper abdominal pain, pharyngitis streptococcal, otitis media, viral gastroenteritis, arthropod bites, and epistaxis.

Limitations of add-on therapies

The six biologics listed here are not indicated for the treatment or relief of acute bronchospasm or status asthmaticus.

Omalizumab and reslizumab have black box warnings for anaphylaxis; healthcare professionals should be prepared to manage anaphylaxis associated with their administration, which could be life-threatening.^[][]

Reslizumab is not indicated for other eosinophilic conditions.^[]

Investigational agents

Depemokimab is a humanized anti-IL-5 monoclonal antibody featuring an extended half-life. Unlike other anti-IL-5 monoclonal antibodies, the drug has improved IL-5 affinity.^[]

GSK’s recent phase III study reported positive results from the SWIFT-1 and SWIFT-2 trials, which evaluated the effectiveness of depemokimab for treating severe asthma with type 2 inflammation. The trials demonstrated that depemokimab significantly reduced the annual rate of asthma exacerbations compared to placebo, with similar safety profiles between the two groups. Depemokimab is notable for being the first ultra-long-acting biologic for severe asthma, allowing for dosing every 6 months.