In recent years, advances in knowledge of molecular mechanisms involved in asthma have changed uncontrolled severe asthma (USA) treatment, with the appearance of biological treatment. USA is a heterogeneous entity with different endotypes and phenotypes. Nowadays, the biological drugs approved with asthma indication are omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. Tezepelumab is approved by the Food and Drug Administration (FDA) in the United States and, recently, by the European Medicines Agency (EMA). All these biological drugs have shown their efficacy in clinical trials, especially in reducing exacerbations, improving asthma control, quality of life, pulmonary function, and withdrawing systemic corticosteroids or at least reducing their daily dose, with some differences between them. Except for mepolizumab and reslizumab, biological drugs have different targets and thus different therapeutic indications should be expected; however, in some patients, more than one drug could be indicated, making the election more difficult. Because there are no direct comparisons between biological drugs, some biomarkers are used to choose between them, but they are not unbeatable. In this article, an algorithm to choose the first biological drug in a specific patient is proposed based on different study results and patient’ characteristics.

Corrigendum: Uncontrolled severe T2 asthma: Which biological to choose? A biomarker-based approach

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare type of anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) with unique features, such as involvement of eosinophils in the pathogenesis, which requires different therapies from those used for other AAV. Conventional treatment includes glucocorticoids (GC) and immunosuppressants. GC are the cornerstone of the initial treatment of EGPA, but relapses are frequent. Cyclophosphamide is typically used in combination with GC for patients with life- and/or organ-threatening disease manifestations. Azathioprine and methotrexate are recommended to maintain remission after induction with cyclophosphamide or as a GC-sparing agent. Nowadays, a better comprehension of the physiopathology of EGPA has opened new therapeutic targets, such as interleukin-5, which has a key role in the refractory disease, relapses, and GC dependence, especially for asthma manifestations. Mepolizumab is the first anti-IL5 antibody approved to treat EGPA. Another anti-IL5 monoclonal antibody, reslizumab, and an anti-IL5 receptor monoclonal antibody, benralizumab, are now being investigated for EGPA.

Background: The GALERNA study is a retrospective real-world observational study conducted across 21 hospitals in Spain, aiming to evaluate long-term clinical benefits and adherence to benralizumab in 255 adult patients with severe eosinophilic asthma (SEA) over a follow-up period of up to 144 weeks. Objectives: Primary objectives focused on assessing adherence to benralizumab, while secondary objectives included the description of severe asthma exacerbation rates, systemic corticosteroid (SCS) use, persistence to benralizumab, lung function, asthma control, and the proportion of patients achieving super-response or clinical remission. Data were collected at baseline (48 weeks prior to benralizumab initiation/index date), follow-up 1 (FUP1) (0–48 weeks), FUP2 (49–96 weeks), and FUP3 (97–144 weeks) after the index date. Results: At baseline, patients demonstrated a substantial disease burden characterised by impaired lung function, poorly controlled asthma, and frequent severe exacerbations. The results indicated high adherence rates to benralizumab, with 92.9% of patients receiving each of the prescribed doses of benralizumab at week 48 and 70.6% at week 144. Patients showed substantial and sustained clinical improvements, with a reduction in the proportion of individuals presenting at least one severe exacerbation from baseline to FUP3 and a 74% decrease in SCS use for the same period. Lung function also improved, with the proportion of patients achieving pre-bronchodilator FEV₁ ≥ 80% rising to 52% at 144 weeks. Furthermore, mean Asthma Control Test (ACT) scores increased to 20.5, with 68.5% of patients achieving well-controlled asthma (ACT ≥ 20). By the end of the study, 63.6% of patients achieved super-response and 39.1% showed clinical remission, with an overall benralizumab persistence of 79.8% during all follow-up periods. Conclusions: The GALERNA study provides compelling real-world evidence that benralizumab affords marked and sustained clinical benefits together with high long-term adherence in Spanish SEA patients, reinforcing its usefulness as a long-term therapeutic option in routine clinical practice.