The Specialist Forum May 2017 | Page 16

www.specialistforum.co.za PULMONOLOGY 3.1.5 Other long term treatment options Immunotherapy Consider stepping down when asthma symptoms have been well controlled and lung function has been stable Allergen immunotherapy should be considered for patients who have persistent asthma if there is clear evidence of a relationship between symptoms and exposure to an allergen to which the patient is sensitive. Both subcutaneous and sublingual immunotherapy has an effect on inflammatory parameters and bronchial hyperreactivity in asthmatics sensitised to house dust mites. Sublingual immunotherapy is the safer option and could be used as adjunctive treatment to pharmacotherapy in adults and children older than five years old with rhinitis and mild to moderate asthma (FEV1 >80%), to enhance asthma control. Immunosuppressives including methotrexate may rarely be of benefit in refractory asthmatics. Patients considered for this treatment must be referred to a specialist. Antihistamines are ineffective in the treatment and prevention of asthma. Dietary changes There is little scientific evidence that exclusion diets are useful in the treatment of asthma. As such, they are not routinely recommended. Several cross-sectional studies have shown that low serum levels of Vitamin D are linked to impaired lung function, higher exacerbation frequency and reduced corticosteroid response. However, to date, Vitamin D supplementation has not been associated with improvement in asthma control or reduction in exacerbations. 4. “Newer” treatment modalities for asthma 4.1 Long Acting Anti-Cholinergics Tiotropium bromide is an inhaled, once daily anticholinergic bronchodilator which binds to all three 16 | May 2017 muscarinic receptors to produce a long acting bronchodilator effect and possibly an anti-inflammatory effect. It was initially approved for COPD, but recently (2015) added on as a late step in adult chronic asthma guidelines as a treatment option in patients with uncontrolled asthma despite high doses of inhaled corticosteroids and LABAs. Tiotropium is available as a dry powder inhaler or pMDI, and is licensed for adults and adolescents over the age of 12 years in a once daily dose. Studies have shown an improvement in lung functions and a reduction in exacerbations in patients with uncontrolled asthma. 4.2 Monoclonal antibodies 4.2.1 Omalizumab (anti IgE) Omalizumab is a recombinant humanised monoclonal anti- IgE antibody. It binds free IgE in blood and interstitial fluid and to the membrane-bound form of IgE on the surface of mIgE- expressing B-lymphocytes. It is licensed as an add-on treatment in severe persistent asthma in adults, adolescents and children over the age of six years with evidence of allergic sensitisation and IgE levels of up to 1500 kU/L. There is also some evidence for its efficacy at higher IgE levels. Studies have shown improvement in quality of life as well as reductions in severe exacerbations in patients on omalizumab. Omalizumab is given subcutaneously every 2-4 weeks and courses of at least six months are recommended for severe asthma in suitable patients. 4.2.2 Mepolizumab (anti interleukin-5) Mepolizumab is a fully humanised anti-interleukin 5 (IL-5) monoclonal IgG1 antibody that binds to free IL5 and prevents its association with the IL5 receptor on eosinophils. In clinical trials it has been shown to reduce airways and blood eosinophils and reduce asthma exacerbations. Mepolizumab has recently been added on to the step-up guidelines for severe asthma uncontrolled on high dose inhaled steroids and LABAs. It should be given in specialist referral centres only and is licensed for over the age of 12 years. 4.2.3 Dupilumab (anti interleukin 4) Dupilumab is a fully human monoclonal antibody directed against the body’s interleukin (IL)-4 receptors, intended to inhibit the downstream effects of type 2 mucosal immunity cytokines, IL-4 and IL-13. Both are cytokines believed to play a major role in the manifestation of allergic diseases. Studies have shown dupilumab to be efficacious as an add-on therapy to medium-to-high-dose inhaled corticosteroids plus a long- acting β 2 agonist in patients with uncontrolled persistent asthma. Improvement has been demonstrated in baseline forced expiratory volume in 1 s (FEV 1 ), as well as a reduction in annualised exacerbation rates and improvements in quality of life and asthma control. Efficacy was more evident when injections were given every two weeks compared with every four weeks. Treatment algorithms for the management of chronic asthma in accordance with GINA (Global Initiative for Asthma) guidelines 2016 are advised. 5. Stepping down asthma treatment Consider stepping down when asthma symptoms have been well controlled and lung function has been stable for three or more months. This should be done under close supervision. Asthma is considered well controlled if: » ≤ 2 daytime symptoms/week » No limitation of activities » No nocturnal symptoms/ awakenings The Specialist Forum | Vol. 17 No. 4