PART I

Part I

Part I

Chapter I: Introduction

Asthma is a serious health problem that affects people of all ages throughout the world. The Global Initiative for Asthma (GINA) treatment guidelines emphasize that clinical management should be based on clinical control rather than asthma severity, which can change over time. Asthma control is defined in the latest update of the GINA guidelines (2007) as no daytime symptoms, no limitations of daily activities, no nocturnal symptoms, no need for reliever treatment, normal or near-normal lung function and no exacerbations. (Robinson 2003 478-483) GINA guidelines recommend that controller medications, i.e. daily treatment to keep asthma under control, be tailored for each patient in a stepwise approach (Fig. 1). Reliever medications, i.e. those that act quickly to reverse bronchoconstriction and relieve its symptoms, are used on an as-needed basis.

Figure 1. The GINA guidelines recommend a stepwise approach to controller medication based on level of control.7 aPreferred controller options as shown in shaded boxes; bReceptor anatagonists or synthesis inhibitors. ICS, inhaled corticosteroid; LABA, long-acting ß2-agonist.

Although mild and moderate persistent asthma can generally be controlled with inhaled corticosteroids (ICS) and long-acting ß2-agonists (LABAs), severe persistent asthma is often inadequately controlled despite these treatments. Furthermore, many patients with severe asthma still fail to achieve complete control despite using additional controller medications, such as leukotriene modifiers (LTRAs) or theophylline. In the Gaining Optimal Asthma Control (GOAL) study, 38% of patients with the most severe asthma (defined as a daily dose of 500-1000 µg beclometasone; n = 568) remained inadequately controlled despite optimized treatment with ICS and a LABA (fluticasone and salmeterol). In addition, 31% of patients still remained inadequately controlled despite the addition of a 4-week course of oral corticosteroids (OCS) to the treatment regimen on completion of the 1-year study. (Nopp and Oman 2007 1175-1181) In an observational study (Epidemiological Study of Xolair Evaluating Clinical Effectiveness and Long-Term Safety in Patients with Moderate-to-Severe Asthma [EXCELS]) of the long-term clinical safety and effectiveness of the anti-immunoglobulin E (anti-IgE) antibody, omalizumab, the entry characteristics of the 5067 patients in the omalizumab cohort with moderate or severe allergic asthma were analysed using the asthma control test (ACT; a 5-item, self-administered survey designed to provide a broad assessment of asthma control over the previous 4 weeks). The scores showed that asthma was well controlled in less than half of patients (45%), while 29% were not well controlled and 26% were poorly controlled. (Humbert 2009 81-84)

Patients with severe asthma are at a high risk of asthma-related hospitalization and mortality. In addition, both impairment in quality of life and economic burden increase with increasing asthma severity and are greatest in patients with inadequately controlled severe persistent allergic asthma. In 1998 in a northern area of Spain, it has been estimated that severe asthma accounted for at least half of the direct and indirect costs associated with asthma. There is, therefore, an urgent need for improved treatment options that will provide asthma control in these patients. (Juniper and Guyatt 1991 77-83)

Based on findings from a European cross-sectional observational study (ENFUMOSA), approximately 50% of ...