Omalizumab for severe asthma: toward personalized treatment based on biomarker profile and clinical history

Abstract

Asthma is a heterogeneous syndrome with numerous underlining molecular and inflammatory mechanisms contributing to the wide spectrum of clinical phenotypes. Multiple therapies targeting severe asthma with type 2 (T2) high inflammation are or soon will be available. T2 high inflammation is defined as inflammation associated with atopy or eosinophilia or an increase in cytokines associated with T-helper 2 lymphocytes. Omalizumab is a humanized anti-IgE monoclonal antibody and the first biologic therapy approved for moderate–severe allergic asthma. Despite the specificity of biologic therapies like omalizumab, clinical response is variable, with approximately 50% of treated patients achieving the primary outcome. A prior identification of the ideal candidate for therapy would improve patient outcomes and optimize the use of health care resources. As the number of biologic therapies for asthma increases, the goal is identification of biomarkers or clinical phenotypes likely to respond to a specific therapy. This review focuses on potential biomarkers and clinical history that may identify responders to omalizumab therapy for asthma.

Omalizumab, the first available antibody for biological treatment of severe asthma: more than a decade of real-life effectiveness

“… 85 Indeed, the EXTRA study has shown that high levels of peripheral blood eosinophils, together with the overexpression of other two biomarkers such as FeNO and serum periostin, can be considered as reliable indicators of type-2 asthmatic inflammation, capable of predicting a good therapeutic effect of omalizumab consisting of marked reductions in asthma exacerbation rates. 101 , 102 However, a very recent retrospective real-life study demonstrated, in patients with severe allergic asthma, that the therapeutic response to omalizumab was similar in patients with relatively high (⩾300 cells/µl of blood) or low ( < 300 cells/µl of blood) pretreatment blood eosinophil numbers. 103 As an add-on biological therapy, omalizumab might be also administered concomitantly with allergen-specific immunotherapy (AIT).…”

<p>FENOMA Study: Achieving Full Control in Patients with Severe Allergic Asthma</p>

“…10 Similar to sputum and blood eosinophils, elevated FeNO is predictive of asthma exacerbations and asthma severity. 8 In fact, FeNO levels before treatment were above the threshold of 25 ppb (FeNO levels <25 ppb are considered normal in adults) 15 (median of 36.0 [23.0; 53.0] ppb). This observation is in agreement with the findings of a prospective, randomized, placebocontrolled study showing that patients with severe asthma and higher baseline FeNO had a greater reduction in exacerbation rate with omalizumab vs. patients with low baseline FeNO.…”

“…1,3,6 Allergic asthma accounts for most cases of asthma, with immunoglobulin E (IgE) being integral to its physiopathology. 7,8 Allergic asthma is associated with increased levels of circulating total and specific IgE, with a clear involvement both at the onset of the disease and during its chronic phase. 7 Omalizumab, the first treatment addressing the allergic component of moderate-to-severe allergic asthma, 9 is an anti-IgE monoclonal antibody that selectively binds to human IgE and prevents its binding to high-affinity IgE receptors.…”

“…in whom omalizumab was strictly administered following therapeutic indication 10 -who participated in the FENOMA study. Treatment-response biomarkers such as total IgE, peripheral blood eosinophil count and exhaled nitric oxide fraction (FeNO) 8,15 were also assessed.…”

Two decades with omalizumab: what we still have to learn

“…In particular, two biomarkers clearly related to asthma severity have been proposed: blood levels of eosinophils and fractional exhaled nitric oxide. 23 In a prospective real-world study of 801 patients with asthma receiving omalizumab, 622 completed the study. Treatment was successful (as assessed by a reduced prevalence of exacerbation and hospitalizations, as well as improved ACT scores), but a significant correlation with biomarker status was not detected.…”