HPE Alpha 1 Antitrypsin Deficiency - Page 14

even asthma, leading to an average delay of almost six years between the onset of symptoms and the final diagnosis. 4 Although some patients present with normal lung function at the time of diagnosis, AATD is associated with increased risk of emphysema and liver disease, namely cirrhosis and hepatocellular carcinoma. Therefore, an early and correct diagnosis may potentially enable an adequate monitoring of these associated conditions, thus preventing further tissue injury. 6 Better awareness by primary care providers, who are most likely to be the first to interact with patients with AATD, 7 can potentially be achieved through continuing medical education and dissemination of educational materials adapted to both clinicians and patients. 5 General practitioners might not always include AATD testing in the assessment of COPD patients, and patients may have to see more than one clinician before receiving a correct diagnosis. 7 Reminders and warning systems to physicians in electronic health records that recommend testing for patients with specific results in lung function tests, as well as clarification of patient selection criteria for screening and treatment and the elimination of obstacles regarding the laboratory testing process (for Analyses of patient registries in example, distribution different countries have shed light on of free diagnostic kits, screening campaigns) the natural history of the disease and the creation of its diverse impact on long-term health and incentives for testing, status and QoL scores can help overcome the current challenges seen in AATD diagnosis. 5 Health care policies and services can also pose obstacles to uniform and equitable access to care for AATD patients, hence the importance of professional associations and regulatory entities in the development of evidence-based and country- appropriate clinical practice guidelines and health policies having the ultimate goal of enabling the collection of meaningful data and patient access to existing and new cost-effective and safe therapies. 3 Impact of the disease on daily activities and health-related QoL Being a hereditary and progressively debilitating disorder, AATD is necessarily associated with the psychological burden of uncertainty about prognosis, which can potentially result in worsening of emotional and physical symptoms, depression and/or anxiety, and overall reduction in quality of life. 8 A cross-sectional study evaluated the role of social environment for 462 patients with COPD associated with AATD and showed that disease uncertainty is reduced by higher quality of support provided by families and social networks and the availability of patient support groups, but increased by having relatives with similar condition(s). 9 It is well known that patient-reported outcomes such as health-related quality of life (HRQoL) measures correlate with the extent of airway obstruction and disease severity in COPD, and they are now recognised as a relevant factor in the evaluation of the disease’s burden because they can accurately predict prognosis. 10,11 In AATD, high exacerbation rates contribute to frequent absences from work and physical limitations in performing routine tasks, and smoking and occupational exposure to dust and fumes can further contribute to their increased frequency. 12 14 | 2019 | hospitalpharmacyeurope.com Analyses of patient registries in different countries have shed light on the natural history of the disease and its diverse impact on long-term health status and QoL scores. 3 In an analysis of 868 adult patients with severe AATD and asymptomatic patients with a protease inhibitor ZZ genotype (which represents the majority of patients with AATD) included in the German AATD registry, data collected over a period of seven years provided important information about deterioration of HRQoL as measured with the St George’s Respiratory Questionnaire (SGRQ). Worsening of scores in the SGRQ was significantly correlated with increased frequency of annual self-reported exacerbations, and significant correlations between SGRQ scores at baseline with smoking habits and the diffusing capacity of the lungs for carbon monoxide were also observed. Moreover, a higher exacerbation rate showed a greater effect specifically on the SGRQ impact score, which assesses impact on employment and daily activities, whereas smoking was strongly associated with the physical activity component of the assessment tool. 13 A large ongoing cross-sectional, prospective study (NCT01245933; https://clinicaltrials.gov/ ct2/show/NCT01245933) involving 2741 patients in the German COPD cohort COSYCONET aims to determine the prevalence and severity of extra-pulmonary conditions and their impact on morbidity and mortality, including hospitalisation rates. A comparative analysis of COPD patients with or without AATD showed that presence of AATD results in generic and disease-specific HRQoL measures, as assessed by the SGRQ and the COPD Assessment Test, that are similar to those of patients without AATD despite lower overall health care resource utilisation and medication burden. 14 Effect of AATD therapies on health status The use of bronchodilators and corticosteroids can effectively ameliorate dyspnoea and improve exercise capacity, but these drugs do not actually have an effect on the increased risk of emphysema seen in patients with AATD. 4 Most of the treatment options available for AATD are those also used in patients having COPD, with the exception of administration of weekly intravenous infusions of purified Alpha 1 Antitrypsin (AAT) preparations, obtained through the pooling of human plasma from healthy donors. Such therapy has been shown to slow lung function decline and organ damage in several randomised and observational studies and is suitable for patients with documented emphysema. 15 The evaluation of the clinical efficacy of AAT therapy may be challenging when forced expiratory volume and mortality are used as primary outcome measures in clinical trials. Improvement in exacerbations and survival rates have also been used as efficacy endpoints, but they have lower sensitivity than standard measures of pulmonary function, and also requires long follow-up periods and large sample sizes in order to adequately power studies to detect significant differences, which is not always feasible in AATD owing to the rarity of the disease. In addition, prolonged use of the placebo comparator raises concerns when an effective drug is available on the market. 4,16 Despite its proven clinical benefits, treatment is not curative but improves or stabilises the irreversible process of loss of lung tissue and the progression of emphysema. Regrettably, the treatment is not available worldwide and is relatively expensive, with total costs depending on the patient’s body weight and on other factors such