Combination of Biological Therapy in Severe Asthma: Where We Are?

Abstract

Biological drugs have revolutionized the management of severe asthma. However, a variable number of patients remain uncontrolled or only partially controlled even after the appropriate administration of a biologic agent. The combination of two biologics may target different inflammatory pathways, and it has been used in patients suffering from uncontrolled severe asthma with evidence of both allergic and eosinophilic phenotypes or severe asthma and type2 comorbidities. Combination therapy has also been used to handle anti-IL4/13R induced hypereosinophilia. There is insufficient data on combining biologics for the treatment of severe uncontrolled asthma and type 2 comorbidities, also because of the high cost, and currently no guideline recommends dual biologic therapy. A systematic search was performed using the Medline and Scopus databases. Published data on concurrent administration of two biological drugs in severe, uncontrolled asthma patients has been reported in 28 real-world studies and 1 clinical trial. Data extraction was followed by a descriptive and narrative synthesis of the findings. Future studies should be conducted to further assess the safety, efficacy, and cost-effectiveness of this therapeutic strategy.

Keywords: biologics; combination biologic therapy; dual biologic therapy; severe asthma; type 2 comorbidities.

Figure 1

PRISMA 2020 Flowchart Diagram of the selected articles.

Figure 2

Approved indications of asthma biologic agents and possible combination strategies, according to patient phenotype and comorbidities.