When to initiate biologics (biological medications) in a patient with asthma?

From the Guidelines

Biologics should be considered for asthma patients with severe, uncontrolled asthma despite adherence to high-dose inhaled corticosteroids (ICS) plus a long-acting beta-agonist (LABA), and who have had at least two exacerbations in the previous year requiring oral corticosteroids, as recommended by the most recent guidelines 1. The specific biologic chosen depends on the patient's asthma phenotype.

• For allergic asthma with elevated IgE levels, omalizumab (150-375 mg subcutaneously every 2-4 weeks) is appropriate, as it has been shown to reduce the incidence of asthma exacerbations, even among patients with more severe asthma 1.
• For eosinophilic asthma (blood eosinophil count ≥300 cells/μL), options include mepolizumab (100 mg subcutaneously monthly), benralizumab (30 mg subcutaneously every 4 weeks for 3 doses, then every 8 weeks), dupilumab (200-300 mg subcutaneously every 2 weeks), or reslizumab (3 mg/kg IV every 4 weeks), as these agents have been demonstrated to reduce eosinophilic inflammation and improve asthma control 1. Before starting biologics, it is essential to:
• Confirm the asthma diagnosis
• Assess adherence to current therapy
• Address comorbidities
• Optimize inhaler technique Biologics work by targeting specific inflammatory pathways: anti-IgE antibodies block allergic responses, while anti-IL5/IL4/IL13 agents reduce eosinophilic inflammation. Treatment response should be evaluated after 4-6 months, looking for reduced exacerbations, decreased oral corticosteroid use, improved lung function, and better symptom control, as recommended by recent guidelines 1.

From the FDA Drug Label

The efficacy of FASENRA for the add-on maintenance treatment of severe asthma, and with an eosinophilic phenotype was evaluated in two randomized, double-blind, parallel-group, placebo-controlled, exacerbation trials, SIROCCO (NCT01928771) and CALIMA (NCT01914757), for 48 and 56 weeks in duration, respectively Patients were required to have a history of 2 or more asthma exacerbations requiring oral or systemic corticosteroid treatment in the past 12 months, ACQ‑6 score of 1. 5 or more at screening, and reduced lung function at baseline [pre-bronchodilator FEV1 below 80% in adults, and below 90% in adolescents] despite regular treatment with high dose ICS (SIROCCO) or with medium or high dose ICS (CALIMA) plus a long-acting beta agonist (LABA) with or without oral corticosteroids (OCS) and additional asthma controller medications Patients were stratified by geography, age, and blood eosinophils count (≥300 cells/μL or <300 cells/μL).

Key Points:

• Patients should have a history of 2 or more asthma exacerbations requiring oral or systemic corticosteroid treatment in the past 12 months.
• Patients should have an ACQ-6 score of 1.5 or more at screening.
• Patients should have reduced lung function at baseline despite regular treatment with high dose ICS or medium or high dose ICS plus a LABA.
• Blood eosinophil count should be ≥300 cells/μL.

Decision: Start an asthma patient on biologics such as benralizumab if they have severe asthma with an eosinophilic phenotype, a history of 2 or more asthma exacerbations in the past 12 months, an ACQ-6 score of 1.5 or more, and reduced lung function despite regular treatment with high dose ICS or medium or high dose ICS plus a LABA, and a blood eosinophil count of ≥300 cells/μL 2.

From the Research

Determining the Appropriate Time to Initiate Biologics in Asthma Patients

• Asthma patients who require high-dose inhaled corticosteroids, with or without add-on treatments, to maintain asthma control may be considered for biologic therapy 3.
• The decision to start biologics should be based on the patient's asthma phenotype, with severe allergic asthma and severe eosinophilic asthma being two defined phenotypes for which targeted biologic therapies are available 4.
• Patients with difficult-to-treat asthma, characterized by poor symptom control or frequent exacerbations despite adherence to inhaled corticosteroid therapy, may benefit from biologic agents 5.
• Biologics such as omalizumab, mepolizumab, benralizumab, and dupilumab have been shown to reduce the need for oral corticosteroids, exacerbation rate, and improve patient-related outcomes in severe asthma patients 3, 6.

Assessment and Referral Pathways

• Patients with severe asthma should be assessed for adherence to medications, confounding factors, and comorbidities before initiating biologic therapy 4, 5.
• Referral to specialized severe asthma centers may be necessary for optimal management and access to biologic therapies 3, 4.
• The use of biomarkers such as blood eosinophil counts and fractional exhaled nitric oxide can inform treatment decisions and guide the selection of biologic agents 4, 6.

Treatment Outcomes and Efficacy

• Biologic therapies have been shown to improve clinical outcomes, including exacerbation rate, oral corticosteroid usage, forced expiratory volume in 1 second, and fractional exhaled nitric oxide, in severe asthma patients 6.
• The introduction of biologics can reduce the annualized exacerbation rate and improve lung function, with effect sizes similar to those observed in randomized controlled trials 6.
• Combination biologic therapy may be beneficial for patients with uncontrolled severe asthma, with some studies demonstrating improved outcomes with the addition of a second biologic agent 7.