D3.175 - Algorithm for Biologics Selection in Severe Asthma

With the advent of targeted therapy, new opportunities have opened up in the treatment of Severe asthma. Understanding the mechanisms of the pathogenesis of the disease for each patient is the basis for a rational and personalized approach to drug selection.

This algorithm was developed based on the medical records analysis of and prescribing various biologics to 256 patients with severe asthma who were monitored for 3-7 years (from 2017 to 2025).

Important laboratory parameters considered as biomarkers of eosinophilic inflammation are peripheral blood eosinophilia and sputum eosinophilia. The level of eosinophils in the blood > 150 cells/mcl is a prognostically favorable factor when prescribing anti-IL-5/anti-IL-5Ra-MAT, while their greatest antieosiphilic action is achieved in patients with blood eosinophilia > 450 cells/mcl. It should also be borne in mind that dupilumab (anti-IL-4Ra-MAT) blocks key reactions that promote the migration of eosinophils to target organs, and its use may lead to an increase of eosinophilia. In this regard, for prescribing dupilumab the initial level of eosinophils should be < 1,000 cells/mcl, and regularly monitored during subsequent administration. With an initially high level of eosinophilia (>1,500 cells/mcl), additional examination is recommended (to exclude parasitic invasions, fungal infections, systemic vasculitis, as an eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, eosinophilic leukemia and other conditions leading to hypereosinophilia. For patients with atopic phenotype, the level of total IgE is assessed. Omalizumab may be prescribed at a total IgE level of 30-1,500 IU/ml. The value of total IgE < 30 IU/ml is a prognostically unfavorable marker of the effectiveness of anti-IgE therapy. In turn, at an IgE level ≥ 1,500 IU/ml, as well as at a patient's body weight > 150 kg (IgE > 1,000 IU/ml, body weight > 60 kg), it is not possible to calculate the dose of omalizumabe. Tezepelumab can be recommended regardless of the initial level of eosinophilia, as well as the presence or absence of atopy.

This algorithm, based on simple clinical criteria, taking into account the prevailing mechanism of pathogenesis and the presence of comorbidities, simplifies the selection of biological drugs in routine clinical practice.