COPD, 12:233–239, 2015 ISSN: 1541-2555 print / 1541-2563 online Copyright © Informa Healthcare USA, Inc. DOI: 10.3109/15412555.2014.933795

ORIGINAL RESEARCH

Determinants of Long-Term Persistence with Tiotropium Bromide for Chronic Obstructive Pulmonary Disease

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Kyuto Tanaka,1,2 Nobufumi Kamiishi,1 Jun Miyata,1 Hiroki Kabata,1 Katsunori Masaki,1 Hiromi Ogura-Tomomatsu,1,3 Katsuyoshi Tomomatsu,1,3 Yusuke Suzuki,1 Koichi Fukunaga,1 Koichi Sayama,1,2 Tomoko Betsuyaku,1 and Koichiro Asano1,3 1

Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

2

Kawasaki Municipal Hospital, Kanagawa, Japan

3

Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan

Abstract Tiotropium bromide, a long-acting anticholinergic agent, improves pulmonary function and quality of life of patients suffering from chronic obstructive pulmonary disease (COPD). We retrospectively examined the factors that determine the longterm persistence with tiotropium bromide. Among 6,301 patients who underwent pulmonary function tests in our pulmonary clinic between 2006 and 2009, 644 met the following criteria: 1) age > 40 years, 2) ≥ 20 pack-years smoking history, and 3) forced expiratory volume in 1 sec / forced vital capacity ratio < 0.7. The clinical information, including the prescription of tiotropium, was obtained from the patients’ records. Tiotropium was administered to 255 patients (40%), of whom 48 (19%) discontinued treatment within 1 year, and 65 (25%) discontinued treatment within the median observation period of 32 months. The drug was discontinued because of ineffectiveness in 35 patients (73%), and because of adverse drug effects in 13 patients (27%). Young age, current smoking, absence of respiratory symptoms alleviation, and less severe disease characterized by a) mild airflow limitation, b) mild to moderate emphysema, or c) no exacerbation of COPD during the 1st year of treatment were predictors of drug discontinuation.

Introduction

Keywords: anticholinergic therapy, long-term therapy, tachyphylaxis, treatment effectiveness, treatment tolerability Correspondence to: Koichiro Asano, MD, Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan, phone: +81-463-93-1121, fax: +81-463-93-0381, email: [email protected]

Tiotropium bromide, a long-acting anticholinergic agent, improves pulmonary function and quality of life, slows the progression of disease, and lowers the rates of disease exacerbation and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) (1–7). In addition, its adverse effects are relatively mild (5). Therefore, in the clinical guidelines issued by the Global Initiative for Chronic Obstructive Lung Disease, tiotropium bromide has been placed on the frontline of pharmacotherapy for patients presenting with symptomatic COPD (8). However, high rates of treatment discontinuation have been reported during long-term management of COPD (9). Even during clinical trials, despite the strong motivation of participants and caregivers to continue the study medication, the reported rates of tiotropium bromide discontinuation have ranged between 16 and 42% (5, 10, 11). In the UPLIFT study, over one third of nearly 3,000 patients who received tiotropium bromide discontinued the drug during the 4-year study period (5). Although adverse events were the leading cause of premature discontinuation of the drug in clinical trials (5, 10, 11), the determinants of its withdrawal in real-life practice remain poorly known (12–14). 233

234

Tanaka et al. Patients screened n=6,301

Patients with confirmed COPD n=644

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Treated with tiotropium n=255

Tiotropium continued beyond 1 year n=190

Never treated with tiotropium n=389

Lost to follow-up: n=13 Deceased: n=4

st Tiotropium discontinued during 1 year n=48

Figure 1. Flow of patients from initial screening to the final study group assignments.

The aim of this study, conducted in a pulmonary clinic of a tertiary medical centre, was to examine the characteristics of patients treated for COPD with tiotropium bromide, and compare the characteristics of patients who remained on long-term treatment with the patients whose therapy was discontinued.

Patient population and methods Out of 6,301 patients who underwent spirometry between years 2006 and 2009 at the Pulmonary Medicine clinic of Keio University Hospital, we identified 644 who fulfilled the following criteria: 1) age >40 years, 2) ≥ 20 pack-year history of smoking, and 3) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 0.7. We reviewed their medical records and ultimately retained in this analysis the 255 patients who were prescribed and received ≥ 1 dose of tiotropium bromide (Figure 1). The severity of airflow limitation was graded according to the 2009 Global Initiative for Chronic Obstructive Lung Disease classification (8). Clinical information, including smoking habits, modified Medical Research Council dyspnoea scale and other respiratory disease manifestations, body mass index, medication, and longterm oxygen therapy, was obtained from the patient’s medical records. The transcripts of the visits made at 1–3 months intervals between 1 year before the beginning of tiotropium bromide therapy and March 2012, were examined. Patients who, at the first visit after the initiation of tiotropium bromide, answered positively the query “does tiotropium bromide improve your

respiratory symptoms?”, were classified as “responders.” Exacerbation of COPD within 12 months before or after the introduction of tiotropium bromide, defined as worsening of respiratory symptoms requiring 1) treatment with systemic corticosteroids, antimicrobials, or both, or 2) hospitalization, was also recorded. The groups of patients who discontinued therapy or whose physicians discontinued its prescription were compared with the group who remained on long-term treatment. The protocol of this study was approved by the Institutional Review Board of Keio University School of Medicine.

Pulmonary function tests Vital capacity, FVC, and FEV1 were measured using an MFR-8200 electronic spirometer (Nihon Koden, Tokyo, Japan), which met the specifications recommended by the American Thoracic Society (15). Diffusing capacity for carbon monoxide per alveolar volume was measured by a 10-second breath holding, using a Chestac-55V volume-type spirometer (Chest MI Co., Tokyo, Japan). Pulmonary emphysema score Pulmonary emphysematous lesions were identified as low attenuation areas (LAA) on computed tomography scan (ProSeed, GE Healthcare Japan, Tokyo, Japan), and evaluated according to the Goddard classification (16). The whole lung was divided into upper, mid and lower left and right lung fields. LAA were visually scored from 0 to 4 in each field, where grade 0 corresponded to no LAA, grade 1 indicated LAA in up to 25%, Copyright © 2015 Informa Healthcare USA, Inc

Persistence with tiotropium bromide for COPD

Table 1. Characteristics of the study groups Tiotropium bromide

Men

Prescribed (n = 255)

Not prescribed (n = 389)

224 (88)

339 (87)

P ns

72 ± 8

67 ± 10

Determinants of Long-Term Persistence with Tiotropium Bromide for Chronic Obstructive Pulmonary Disease.

Tiotropium bromide, a long-acting anticholinergic agent, improves pulmonary function and quality of life of patients suffering from chronic obstructiv...
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