Anti-IL-5 therapy in patients with severe eosinophilic asthma – clinical efficacy and possible criteria for treatment response

Abstract

BackgroundInterleukin-5 (IL-5) antibodies represent a promising therapeutic option for patients with severe eosinophilic asthma. To date, no official treatment response criteria exist. In this study, simple criteria for treatment response applicable to all asthma patients were used to evaluate clinical efficacy and predictors for treatment response in a real-life setting.MethodsData from 42 patients with severe eosinophilic asthma treated with mepolizumab for at least six months were analysed. Simple criteria to assess treatment response in clinical practice were used: increase of FEV1 ≥ 12% or ≥ 200 ml, reduction of blood eosinophils (< 150/μl or < 80% from baseline) and improvement of subjective condition (patient-judged subjective improvement or worsening following therapy). Patients were considered treatment responders if two criteria were fulfilled.ResultsThirty-two out of 42 patients (76% [61–87%]) were classified as responders. Within the groups (responder vs non-responder), treatment with mepolizumab led to significant increase in FEV1 (+ 600 ml vs -100 ml, p = 0.003), oxygenation (+ 8 mmHg vs -3 mmHg, p = 0.001), quality of life (visual analogue scale; + 28% vs − 5%, p = 0.004) and Asthma Control Test (+ 8 vs + 1 points, p = 0.002). In the responder group a significant decrease in the exacerbation rate over 12 months (1.45 vs 0.45, p = 0.002) was observed. Baseline characteristics (sex, BMI, smoking history, allergies, baseline level of eosinophils) did not predict treatment response.ConclusionUsing improvement of lung function, decrease of eosinophils and improvement of subjective condition as response criteria, 76% of treated patients could be classified as treatment responders, demonstrating the efficacy of anti-IL-5 therapy in clinical practice.

A thymic stromal lymphopoietin polymorphism may provide protection from asthma by altering gene expression

“…Our data illustrate the key role of TSLP genotype in the modulation of asthma disease expression and its management, and the influence of TSLP genetic variation on disease expression/endotype; this is aligned with previous observations on the targeted use of biologics, such as anti‐IL‐5/IL‐5R therapies, in eosinophilic asthma, and the concept of specialized risk stratification and treatment of asthma endotypes.…”

“…Taken together with our current findings on differential responses according to TSLP genotype, the findings of Gauvreau et al 33 and a follow-up larger phase 2b study of asthma suggest that anti-TSLP therapy may be beneficial to select individuals with poorly controlled asthma. 34 Our data illustrate the key role of TSLP genotype in the modulation of asthma disease expression and its management, and the influence of TSLP genetic variation on disease expression/endotype; this is aligned with previous observations on the targeted use of biologics, such as anti-IL-5/IL-5R therapies, in eosinophilic asthma, 35,36 and the concept of specialized risk stratification and treatment of asthma endotypes.…”

One year of mepolizumab. Efficacy and safety in real-life in Italy

“…In Italy, the regulatory Agency requires a minimum threshold of 150 eosinophils/μL before prescription and 300/μL in the previous year, in addition to the clinical criteria of severe asthma [21]. Despite the efficacy of MEP has been largely demonstrated in clinical trials only few data are available in the real-life setting [2,[22][23][24][25]. This retrospective observational study would add further data on the use of MEP in real-life.…”

“…Asthma represents one of the most common worldwide chronic diseases, affecting about 315 million of people [1]. Epidemiological studies show that the severe form of this disease occurs in about 3-10% of asthmatic patients [2]. According to ATS/ERS guidelines [3] severe asthma is characterised by poor control despite the maximal treatment, including high dose of inhaled glucocorticoids (ICS) plus a second controller (usually a long-acting β2-agonist), and/or a long-acting antimuscarinic agent, leukotriene receptor antagonist or theophylline.…”

A Possible Explanation for Non-responders, Responders and Super-responders to Biologics in Severe Asthma

“…Two large studies found that 82-83% of patients are responders to omalizumab and two smaller studies found that 76-77% of patients are responders to mepolizumab. [3][4][5][6] Although, the criteria for responder versus nonresponder differed between these studies, reflecting the consensus statement that several indicators can be used. 2 There are limited explanations for the variable response to biologics.…”