Omalizumab in the management of patients with allergic (IgE-mediated) asthma

Abstract

Immunoglobulin E (IgE) is central to the pathophysiology of allergic asthma. Omalizumab, an anti-IgE monoclonal antibody, binds to the FcɛRI binding site on free IgE. As a result, circulating free IgE is reduced, IgE is prevented from attaching to mast cells and basophils, and FcɛRI receptor expression is down-regulated. The inflammatory response to allergens and the acute and chronic effector phases of allergic inflammation are thereby attenuated. In clinical trials in adults and adolescents, omalizumab reduced asthma exacerbations, severe asthma exacerbations, inhaled corticosteroid requirements, and emergency visits, as well as significantly improving asthma-related quality of life, morning peak expiratory flow and asthma symptom scores in patients with severe allergic (IgE-mediated) asthma. Results from clinical trials in children (<12 years) are consistent with those in the adult population. It is difficult to predict which patients will respond to omalizumab. Responders to omalizumab should be identified after a 16-week trial of therapy using the physician’s overall assessment. When treatment is targeted to these responders, omalizumab provides a cost-effective therapy for inadequately controlled severe allergic (IgE-mediated) asthma. Long-term therapy with omalizumab shows the potential for disease-modification in asthma. Ongoing studies are also evaluating the use of omalizumab in other non-asthma IgE-mediated conditions.

Indirect comparison of bronchial thermoplasty versus omalizumab for uncontrolled severe asthma

“…Moreover, evidence from the early RISA clinical trial [22] and several case series [24][25][26][27][28][29] shows BT to be similarly effective in patients more severely affected by their asthma than those included in the AIR2 trial. On the OM side of the comparison, a pooled analysis of data from seven RCTs involving 4308 patients, 93% of which had severe asthma, has shown that baseline characteristics do not reliably predict benefit with OM, although there was a suggestion of a greater treatment effect in patients with lower percentagepredicted FEV1 values and higher IgE [30][31][32][33], and more recently, in those with a higher serum eosinophil count, serum periostin or fractionated exhaled nitric oxide [34].…”

Novel Therapies in Asthma

“…92,93 There was some suggestion in pooled data from initial trials that there might be an increased risk of malignancy associated with omalizumab therapy, though it could be considered a stretch to attribute a causal relationship of this type in trials that lasted a year or less. 86 Interestingly, when the data were analyzed more closely, the number of cancers in the omalizumab groups in these trials actually matched that of the general population, whereas the placebo groups had an unexplained cancer rate only one-third of what would be expected. 94 Omalizumab is pregnancy category B.…”

“…86 Cell-bound IgE forms crosslinks when exposed to allergens. This leads to degranulation of the mast cell or basophil, releasing histamine and other proinflammatory molecules, precipitating bronchospasm in the asthmatic patient.…”

“…If therapy is stopped, serum IgE and receptor activity return to previous levels fairly quickly, but there is no evidence of a rebound phenomenon. 86,88,89 Adverse reactions and interactions…”

The Differentiation of Chronic Obstructive Pulmonary Disease from Asthma: A Review of Current Diagnostic and Treatment Recommendations

“…Pharmacotherapies that target immunoglobulin E, a key mediator in molecular pathways involved in allergic responses, can be used to manage individuals with severe, persistent disease [33]. Omalizumab, an anti-immunoglobulin E monoclonal antibody, may be prescribed in the United States for asthma patients with “moderate to severe persistent disease who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms cannot be adequately controlled with an ICS” [34].…”