Factors reducing omalizumab response in severe asthma

Abstract

Background: Despite adding Omalizumab to conventional therapy, several severe asthmatics still show poor disease control. We investigated the factors that may affect a reduced Omalizumab response in a large population of severe asthmatics.

Methods: 340 patients were retrospectively evaluated. FEV₁%, FVC%, Asthma Control Test (ACT), fractional exhaled nitric oxide (FENO), possible step-downs/step-ups of concomitant therapies, exacerbations, disease control levels, ICS doses and SABA use, observed at the end of treatment, were considered as a response to Omalizumab.

Results: Age was an independent risk factor for a reduced response concerning FEV₁%, FVC%, ACT and for a lower asthma control. Obesity (vs normal weight) was a determinant condition for exacerbations (OR:3.114[1.509-6.424], p = 0.002), for a disease partial/no control (OR:2.665[1.064-6.680], p = 0.036), for excessive SABA use (OR:4.448[1.837-10.768], p = 0.002) and for an unchanged/increased level of concomitant asthma medications. Furthermore, obesity also reduced the response in FEV₁ (β = -6.981,p = 0.04), FVC (β = -11.689,p = 0.014) and ACT (β = -2.585, p = 0.027) and was associated with a higher FENO level (β = 49.045,p = 0.040). Having at least one comorbidity was a risk factor for exacerbations (OR:1.383[1.128-1.697], p = 0.008) and for an ACT <20 (OR:2.410[1.071-3.690], p = 0.008). Specifically, chronic heart disease was associated with both a lower ACT and FVC% whereas gastroesophageal reflux with a partial/no asthma control. Nasal polyps were a predisposing factor leading both to exacerbations and to the use of higher inhaled corticosteroids doses. Moreover, smoking habits, pollen or dog/cat dander co-sensitizations may negatively influence Omalizumab response.

Conclusion: Age, obesity, comorbidities, smoking habits, nasal polyps, allergic poly-sensitization might reduce Omalizumab effectiveness independently to other asthma-influencing factors.

Keywords: Age; Comorbidities; Obesity; Omalizumab; Real-life; Severe asthma; Therapeutic response.