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Asthma: Newer Tx options mean more targeted therapy

The Journal of Family Practice. 2020 April;69(3):135-144
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It’s an exciting era of asthma management, with the introduction of several novel modalities, including biological therapy and bronchial thermoplasty.

PRACTICE RECOMMENDATIONS

› Consider inhaled corticosteroids (ICS) as your first choice for a long-term control agent to treat asthma; add a long-acting beta agonist (LABA) when needed. A

› Use long-acting muscarinic antagonists (LAMA) as add-on therapy for patients whose asthma is uncontrolled despite the use of low-dose ICS-LABA, or as an alternative to high-dose ICS-LABA. A

› Consider biological therapies for patients with asthma exacerbations that require steroids at least twice a year. B

› Use azithromycin as an add-on therapy to ICS-LABA for a select group of patients with uncontrolled persistent asthma (neutrophilic phenotype). C

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Reslizumab (Cinqair) is a rat anti-human monoclonal antibody of the IgG4κ subtype that binds to a small region of IL-5 and subsequently blocks IL-5 from binding to the IL-5 receptor complex on the cell surface of eosinophils. It is currently approved for use as a 3-mg/kg IV infusion every 4 weeks. In large clinical trials,41-43 reslizumab decreased asthma exacerbation and improved QoL, asthma control, and lung function. Most of the study populations had an eosinophil count > 400 cells/mcL. A small study also suggested patients with severe eosinophilic asthma with prednisone dependency (10 mg/d) had better sputum eosinophilia suppression and asthma control with reslizumab when compared with mepolizumab.44

Benralizumab (Fasenra) is a humanized IgG1 anti-IL-5 receptor α monoclonal antibody derived from mice. It induces apoptosis of eosinophils and, to a lesser extent, of basophils.45 In clinical trials, it demonstrated a reduction in asthma exacerbation rate and improvement in prebronchodilator FEV1 and asthma symptoms.46,47 It does not need reconstitution, as the drug is dispensed as prefilled syringes with fixed non-weight-based dosing. Another potential advantage to benralizumab is that after the loading dose, subsequent doses are given every 8 weeks.

Bronchial thermoplasty

Bronchial thermoplasty (BT) is a novel nonpharmacologic intervention that entails the delivery of controlled radiofrequency-­generated heat via a catheter inserted into the bronchial tree of the lungs through a flexible bronchoscope. The potential mechanism of action is reduction in airway smooth muscle mass and inflammatory markers.

Evidence for BT started with the Asthma Intervention Research (AIR) and Research in Severe Asthma (RISA) trials.48,49 In the AIR study, BT was shown to reduce the rate of mild exacerbations and improve morning peak expiratory flow and asthma scores at 12 months.48 In the RISA trial, BT resulted in improvements in Asthma Quality of Life Questionnaire (AQLQ) score and need for rescue medication at 52 weeks, as well as a trend toward decrease in steroid use.49

Bronchial thermoplasty results in clinically worthwhile reductions in severe exacerbations and ED visits in the year post treatment.

However, these studies were criticized for not having a placebo group—an issue addressed in the AIR2 trial, which compared bronchial thermoplasty with a sham procedure. AIR2 demonstrated improvements in AQLQ score and a 32% reduction in severe exacerbations and 84% fewer ED visits in the post-treatment period (up to 1 year post treatment).50

Continue to: Both treatment groups...