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.

Biological drugs have revolutionized the management of severe asthma, and a tailored treatment approach has made it possible to consider remission as an achievable treatment target. The incidence of autoimmune diseases is increasing worldwide. Patients suffering from severe asthma, eligible for or already treated with an asthma-approved biologic agent, may suffer from another immune-mediated inflammatory disease (IMID) that could require the simultaneous use of a second monoclonal antibody. The real-life studies available in the literature describing the concurrent administration of an asthma-approved biologic agent with another biologic for a different immune disease, obtained through a systematic search on online databases based on monoclonal antibodies, were collected and analyzed. In this review, 26 articles were included according to the prespecified inclusion and exclusion criteria. All included papers were retrospective in nature. Study designs were case reports (n=18), case series (n=3), retrospective chart reviews (n=3), retrospective observational studies (n=1), and cohort studies (n=1). The study is intended to present, within the current literature, all the administered combinations of severe asthma-approved biologics with monoclonal antibodies for a different indication. Those were grouped according to the IMID for whom the second biologic agent, with a different mechanism of action, was prescribed. The combinations prescribed to the cohort of patients specifically treating uncontrolled severe asthma were more deeply evaluated in the discussion section, since an analysis of these therapeutic combinations deriving from real-life experiences may be useful to optimize the management of patients with severe asthma, ultimately leading to improved patient care and outcomes. Prospective registries and future studies are required to assess the safety and efficacy of combination therapies for severe asthmatic patients who suffer from an IMID.