Journal name: Patient Preference and Adherence Article Designation: Review Year: 2015 Volume: 9 Patient Preference and Adherence Dovepress Running head verso: Lopez-Campos et al Running head recto: Aclidinium and patient-reported outcomes open access to scientific and medical research DOI: http://dx.doi.org/10.2147/PPA.S55009 Open Access Full Text Article REVIEW Patient-reported outcomes and considerations in the management of COPD: focus on aclidinium Jose Luis Lopez-Campos1,2 Abstract: Chronic obstructive pulmonary disease (COPD) is a complex heterogeneous disease, Carmen Calero1,2 in which several factors combine to give the final clinical expression. Both early and more 1 recent studies have shown that forced expiratory volume in one second (FEV ), despite being Cecilia Lopez-Ramirez 1 Maria Isabel Asensio-Cruz1 an extremely important parameter to predict the progression of the disease, is a poor surrogate Eduardo Márquez-Martín1 marker for symptoms perception. Accordingly, patient-reported outcomes (PROs) have gained Francisco Ortega-Ruiz1,2 popularity as a measure of the impact of treatment from the patients’ perspective, since they represent the individuals’ perception of their health status, beyond any physiological limitations. 1 Unidad Médico-Quirúrgica de Several such PROs, therefore, are currently included in multidimensional COPD evaluation. Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla This multidimensional approach helps identify different patient types and individualize, up to (IBiS), Hospital Universitario Virgen a certain point, pharmacological treatment. In this multidimensional approach it is important to del Rocío/Universidad de Sevilla, highlight the importance of long-acting bronchodilators in COPD treatment strategies. Long- Sevilla, 2CIBER de Enfermedades Respiratorias (CIBERES), Instituto de acting bronchodilators are cost-effective and have been shown to achieve the greatest functional Salud Carlos III, Madrid, Spain and clinical improvements in COPD. As a result, long-acting bronchodilators are now the main pharmacological treatment for COPD at all stages of the disease. Until recently, tiotropium was the leading bronchodilator for the treatment of COPD. The clinical development of this medi- cation, unprecedented in inhaled therapy, involved tens of thousands of patients and yielded consistent outcomes in terms of lung function, symptoms, quality of life, exacerbations, and prognosis. However, new long-acting bronchodilators have recently been developed or are cur- rently under development. In this review, we evaluate the effects of aclidinium bromide, a novel long-acting bronchodilator, on PROs in COPD. Aclidinium is a novel long-acting muscarinic antagonist with a good safety profile for the treatment of COPD, and has proven efficacy in both objective functional measurements and PROs. Comparison studies with tiotropium have shown it to have similar lung function improvement and a similar impact on PROs, including quality of life or symptom perception. Keywords: patient-reported outcomes, chronic obstructive pulmonary disease, bronchodila- tors, aclidinium Introduction Although recent studies have shown a steady decrease in chronic obstructive pulmonary disease (COPD) mortality,1 it is still the third leading cause of death.2 Additionally, the impact of COPD on health-related quality of life3 and the burden on health care systems4 make it a disease of the first order. Correspondence: Jose Luis Lopez- Campos As an obstructive disease, the main parameter to evaluate progression is the degree Unidad Médico-Quirúrgica de of airflow obstruction measured by the forced expiratory volume in one second (FEV1) Enfermedades Respiratorias, Instituto obtained during a forced spirometry. As a result, traditional clinical trials have focused de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/ on demonstrating improvement in FEV1 either as an isolated measurement or as a Universidad de Sevilla, Avda Manuel declining trend over time.5 Accordingly, previous guidelines focused on establishing Siurot, s/n, 41012 Sevilla, Spain 6 Email [email protected] treatment strategies according to the degree of FEV1 impairment. submit your manuscript | www.dovepress.com Patient Preference and Adherence 2015:9 95–104 95 Dovepress © 2015 Lopez-Campos et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further http://dx.doi.org/10.2147/PPA.S55009 permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Lopez-Campos et al Dovepress However, COPD is a complex heterogeneous disease, Consequently, in recent years, a shift toward patient- in which several factors combine to give the final clinical centered medicine has been proposed, and several initiatives expression. Both early and more recent studies have shown have been put forward to include other clinical variables that, despite being an extremely important parameter to pre- in the so-called multidimensional evaluation of the COPD dict the progression of the disease, FEV1 is a poor surrogate patient, in which FEV1 continues to play a prominent role, marker for symptoms perception. In the Evaluation of COPD but is modulated by other clinical disease expressions.9 Longitudinally to Identify Predictive Surrogate End-points Accordingly, since the 2011 update, the Global initiative (ECLIPSE) study, a large, 3-year observational controlled for chronic Obstructive Lung Disease incorporates a three- multicenter international study aimed at defining clinically pronged approach (lung function, chronic symptoms, and relevant subtypes of COPD,7 the authors very elegantly exacerbations) to identify types of patients who may need 10 11 showed the complex interaction between FEV1 and clinical different treatment strategies. Although controversial, one markers. As a result, although clinical symptoms worsen of the strengths of this approach is the inclusion of patient- as FEV1 decreases in the cohort of patients, when it comes reported outcomes (PROs) as part of the evaluation system. down to the individual patient, the authors found different PROs have gained popularity as a measure of the impact of degrees of impairment in symptoms or exacerbations in treatment from the patients’ perspective, since they represent 8 all FEV1-mediated COPD degrees of severity (Figure 1). the individuals’ experience of their health status, beyond any This suggested that new markers of disease expression and physiological limitations.12,13 This multidimensional approach progression were needed to make a correct and more com- helps identify different patient types and individualize, up to prehensive evaluation of COPD patients. a certain point, pharmacological treatment. (A)(Rho=–0.36 B) Rho=–0.34 P<0.001 P<0.001 1,000 4 800 3 ) 600 2 400 1 6MWD (m mMRC score 200 0 0 0 20 40 60 80 20 40 60 80 Post-dose FEV1 (% predicted) Post-dose FEV1 (% predicted) (C) Rho=–0.21 (D) Rho=–0.38 P<0.001 P<0.001 7 100 e 6 80 5 4 60 3 40 2 1 20 0 SGRQ-C total scor 0 Number of exacerbations 020406080 20 40 60 80 Post-dose FEV1 (% predicted) Post-dose FEV1 (% predicted) Figure 1 Relationship between the severity of airflow limitation and breathlessness as assessed by the mMRC questionnaire (panel A), exercise capacity as assessed by the 6MWD (panel B), reported exacerbations in the year before inclusion in the study (panel C), and health status as assessed by the SGRQ-C (panel D). Notes: Copyright ©2010. Agusti A, Calverley PM, Celli B, et al. Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res. 2010;11:122.8 Abbreviations: mMRC, modified Medical Research Council; SGRQ-C, St George’s Respiratory Questionnaire – COPD specific; 6MWD, 6-minute walking distance. 96 submit your manuscript | www.dovepress.com Patient Preference and Adherence 2015:9 Dovepress Dovepress Aclidinium and patient-reported outcomes In this system, it is important to highlight the impor- colonization, or different tests to identify the Asthma and tance of long-acting bronchodilators in COPD treatment COPD Overlap Syndrome.21,22 However, objective measure- strategies. Long-acting bronchodilators are cost-effective14 ments correlate poorly with the patient’s subjective experi- and have been shown to achieve the greatest functional and ence, and should be complemented by subjective PRO. clinical improvements in COPD.15 As a result, long-acting The term PRO has been coined to describe the patient’s bronchodilators are now the main pharmacological treatment self-perceived health status.13 PROs are outcomes reported for COPD at all stages of the disease.16 directly by patients, usually by means of self-administered Until recently, tiotropium was the leading bronchodilator questionnaires or diaries, or during a structured interview. In for the treatment of COPD. The clinical development of this this way, they capture the individual’s experiences of COPD medication, unprecedented in inhaled therapy, has involved without any interpretation from