Health Concerns

Asthma

Novel and Emerging Asthma Therapies

Suplatast tosilate. The immunological reaction to antigens is driven by two counterbalancing paradigms – Th1 and Th2. In asthma, an imbalance favoring Th2 is observed (Nagai 2012). Suplatast tosilate is a Th2 cytokine inhibitor that has been shown to ease inflammation in asthma and related allergic conditions (Wada 2009; Stokes 2004). Clinical trials with suplatast tosilate have been quite promising. Not only has suplatast tosilate been shown to be at least as effective as some traditional asthma drugs (Shiga 2011), but it also improved lung function in asthmatic subjects who were already being treated with steroids (Tamaoki 2000; Sano 2003) as well as subjects who did not respond to leukotriene receptor antagonists (Wada 2009). Unfortunately, suplatast tosilate is not approved in the United States, but is available in Japan as Tosilart® and IPD Capsules® (Drugs.com 2012).

Biological Agents

Biological agents (biologics) are protein-based products, which include antibodies and recombinant protein-based receptors. Examples include humanized monoclonal antibodies (antibodies manufactured in the laboratory from identical immune cells), which target specific antibodies or cytokines.

Omalizumab (Xolair®). Omalizumab, a monoclonal antibody that inhibits a key mediator of antigen sensitization called immunoglobulin E (IgE), is approved to treat asthma. Omalizumab's cost is high and hence is mainly prescribed for patients with severe, persistent asthma, which cannot be controlled even with high doses of corticosteroids. Adverse effects of omalizumab include severe allergic reactions and cancer (Davydov 2005).

Monoclonal antibodies that target eosinophils. Eosinophils are immune cells that accumulate in sites of asthmatic inflammation and release inflammatory mediators (Walsh 2010; Conroy 2001). Interleukin-5 (IL-5) is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior (Corren 2011). Several humanized monoclonal antibody therapies (e.g., mepolizumab, benralizumab and reslizumab) have selected IL-5 as a potential target to prevent eosinophil-mediated inflammation in patients with asthma (Thomson 2011). In one placebo-controlled trial, mepolizumab was associated with significantly fewer severe exacerbations of eosinophilic asthma than placebo over the course of 50 weeks (Haldar 2009). Mepolizumab also significantly reduced the number of eosinophils in blood and sputum (Haldar 2009; Nair 2009). Another randomized, placebo-controlled trial found that intravenous infusions of reslizumab on poorly controlled eosinophilic asthma were generally well tolerated and reduced sputum eosinophil concentration, improved airway function, and trended toward greater asthma control compared to placebo (Castro 2011).

Pitrakinra (Aerovant®). Interleukin-4 (IL-4) is another important contributor to eosinophil-mediated inflammation (Piehler 2011). In two independent randomized, double-blind, placebo-controlled trials using a drug called pitrakinra (Aerovant®) that blocks the effects of IL-4, researchers were able to significantly relieve asthma symptoms in 28 subjects with allergic asthma compared to 28 subjects who received a placebo (Wenzel 2007).

Bronchial Thermoplasty

Bronchial thermoplasty is a therapy in which radio-frequency energy bursts are used to heat and destroy muscle tissue in the airway, thus hindering the ability of the bronchial tubes to constrict. It is used only for patients with severe refractory asthma. Results from clinical trials have shown that patients who underwent this procedure experienced fewer symptoms, enjoyed better quality of life and needed less emergency room visits (Gildea 2011).

Although bronchial thermoplasty is relatively safe, patients have to be monitored during (for symptoms of asthma and other adverse events) and after treatment because exacerbations can occur up to 6 weeks following the final procedure. The U.S. Food and Drug Administration has approved bronchial thermoplasty for treatment of severe refractory asthma but a follow up of the Phase 4 trial study participants to determine long-term effects of the procedure is still pending (Gildea 2011).