Asthma biologics

Abstract

Although 5 biologic therapies have Food and Drug Administration (FDA)-approved indications for difficult-to-control asthma, the clinical trials that proved the efficacy and safety of these biologics were similar in their inclusion criteria, study protocols, and measured outcomes. Initial trial results are now being reanalyzed and reinterpreted in subsets of patients with asthma that demonstrate enhanced responses. As a result, keeping up with the growing body of literature surrounding asthma biologic therapy has become increasingly difficult. This review summarizes and compares trial designs, patient cohorts, and study results of the major trials involving these therapies. Because of variations in inclusion criteria and natural variations in enrolled cohorts, the baseline clinical traits and severity of study populations in asthma biologic trials have differed significantly. For example, baseline annualized exacerbation rates in the year before enrollment and blood eosinophilia, which are both strong predictors of a biologic's success, differed strongly among populations. Early omalizumab efficacy trials did not stratify subjects by blood eosinophils or include patients taking long-acting beta agonists or oral steroids but showed relative reductions in exacerbation rates comparable to those of the newer asthma biologics among less severe cohorts. If a care provider's aim is to reduce clinically significant exacerbations in a patient with peripheral blood eosinophilia, it is our opinion that dupilumab, mepolizumab, and reslizumab have the strongest supporting data. Mepolizumab has also demonstrated an ability to reduce emergency department visits and hospitalizations. If the goal is to improve lung function, dupilumab therapy has demonstrated the largest numeric improvements in prebronchodilator forced expiratory volume in 1 second (FEV 1) % predicted compared with placebo, with consistent results across all phase II and phase III trials, including its steroid-sparing trial (QUEST LIBERTY VENTURE). Benralizumab also demonstrated improvements in lung function in 2 phase III trials (SIROCCO, CALIMA) and its long-term safety trial (BORA). If the objective is to reduce daily oral steroids, benralizumab and dupilumab have the strongest supporting data, with roughly 50% of subjects in both trials demonstrating an ability to stop steroids altogether. Of note, a strong difference was seen across studies in the ability to reduce steroids among the placebo groups, which makes comparisons between these 3 steroid-sparing trials challenging.

Managing Exacerbations in Thunderstorm Asthma: Current Insights

“…Each biologic has been shown to reduce systemic steroid use, ED visits, and hospitalization. 80 These treatments are targeted towards a TH-2 asthma phenotype, which clearly correlates with the risk profile for SAR with TA. Furthermore, the anti-IgE medication omalizumab has been shown to have increased benefit in autumn and spring (compared with summer months) across all age groups in individuals with allergic asthma in the US.…”

Management of Chronic Rhinosinusitis with Nasal Polyposis in the Era of Biologics

“…It is marketed under the trade name of Xolair and was originally FDA approved for use for the treatment of moderate to severe persistent allergic asthma in people 6 years of age or older whose asthma symptoms are not controlled by inhaled corticosteroids, and for chronic idiopathic urticaria in people 12 years of age and older. 37 , 38 It is given via a subcutaneous injection every 2–4 weeks with dose determined by serum total IgE and body weight. Its role in CRSwNP was based on literature suggesting a pathophysiologic mechanism related to local intranasal IgE production that leads to an inflammatory cascade.…”

Modulating Th2 Cell Immunity for the Treatment of Asthma

“…The failure of conventional therapies in these corticosteroid-resistant patients justifies looking for new approaches to treat allergic asthma. In this regard, the central role of Th2 cells in regulating airway inflammation has aroused great interest in the therapeutic potential of “ anti-Th2 approaches .” As such, new biological asthma medications based on monoclonal antibodies against key Th2 mediators have been recently approved, and more are being under investigation ( 7 ). Furthermore, allergen immunotherapy, a long-term treatment that inhibits Th2-cell-mediated responses, decreases symptoms for many people with allergy disease ( 8 ), thereby evidencing the central pathogenic role of Th2 cells in the pathophysiology of allergy.…”