Real-world effectiveness of early intervention with fixed-dose tiotropium/olodaterol vs tiotropium in Japanese patients with COPD: a high-dimensional propensity score–matched cohort analysis

Abstract

Background Escalation to triple therapy (long-acting muscarinic antagonist/β2-agonist, inhaled corticosteroid [ICS]) in chronic obstructive pulmonary disorder (COPD) is recommended for patients on LAMA/LABA combinations with frequent exacerbations and severe symptoms. An extended time-to-escalation to triple therapy suggests patients are in a stable condition and is an indicator of treatment effectiveness. No studies in Japanese clinical practice have compared the effectiveness of LAMA/LABA fixed-dose combination therapies with LAMA monotherapy in terms of time-to-escalation to triple therapy. The primary objective of this real-world study in Japan was to compare time-to-escalation to triple therapy among new users of tiotropium/olodaterol or tiotropium monotherapy for COPD without asthma. Methods In this active-comparator cohort study, new users of tiotropium/olodaterol (n = 1436) and tiotropium monotherapy (n = 5352) were identified from a large Japanese hospital-based database (Medical Data Vision Co., Ltd., Tokyo; prespecified study period: 1 April 2015 to 31 March 2019); patients in each group were matched 1:1 using high-dimensional propensity scores (hdPS). The primary outcome was time-to-escalation to triple therapy. Results For the prespecified study period in the hdPS-matched cohort, escalation to triple therapy was infrequent among new users of tiotropium/olodaterol (n = 1302, 7 escalation events) and tiotropium monotherapy (n = 1302, 8 escalation events). The difference in time-to-escalation to triple therapy between groups was not statistically significant (median [interquartile range]: 28 days [15.0–139.2] for tiotropium monotherapy vs 193 days [94.5–302.0] for tiotropium/olodaterol; hazard ratio: 0.89; 95% CI: 0.32–2.46). Similar findings (hazard ratio: 0.71; 95% Cl: 0.36–1.40) were observed in a post hoc analysis, which extended the study period by 1 year to 31 March 2020. Risks of first moderate and/or severe COPD exacerbation were lower for tiotropium/olodaterol than tiotropium monotherapy (between-group differences not significant). There were no significant between-group differences for the risks of all-cause inpatient mortality, major adverse cardiovascular events, and first use of home oxygen therapy. Conclusions ICS monotherapy or ICS/LABA added to tiotropium or tiotropium/olodaterol is limited in Japanese clinical settings. The number of escalations to triple therapy was very limited in the dataset and there was insufficient power to detect differences between the treatment groups in the primary hdPS-matched cohort.

Effect of timing of bronchodilator therapy initiation on exacerbations in patients with chronic obstructive pulmonary disease: a retrospective cohort study

“…Healthcare professionals rely on spirometry to confirm a diagnosis of COPD [ 29 ]; therefore, the timing of therapy initiation may be affected by the specialty of the treating physician. The rates of moderate or severe exacerbations among patients analyzed in our cohort were consistent with those described previously in the Japanese population [ 25 , 26 , 30 ]. The incidence of COPD exacerbations may be lower in Japan than in other countries because Japanese physicians often use asthma-COPD overlap as a disease label, resulting in an underreporting of the incidence of COPD exacerbations [ 30 ].…”

“…The baseline sociodemographic characteristics of the patients included in the present cohort were consistent with those in previous studies [ 25 , 26 ], although the prevalence of each comorbidity was lower than that described previously in the Japanese population [ 27 ]. Since the current database only includes registered facilities, information regarding comorbidities may not be available for patients if they were diagnosed or received treatment at non-registered facilities.…”

Patient and Therapeutic Profiles of Pulmonary Hypertension in Chronic Lung Diseases in Japan: A Cohort Study Using a Claims Database

“…For example, a registry study by Tanabe et al [ 11 ] on patients with PH associated with respiratory disease had a population with a mean age of 67 ± 11 years and was 70% male. Other studies using data extracted from the MDV database in Japan on patients with idiopathic pulmonary fibrosis and COPD also estimated a high percentage of elderly patients and a predominantly male population which is in line with our study [ 22 , 28 ]. Our findings are consistent with studies using the COMPERA registry which involved elderly patients [ 6 , 29 , 30 ] as well as another recently published study using data from both the COMPERA and ASPIRE registries [ 30 ] which partially observed patients (patients with idiopathic pulmonary artery hypertension (IPAH) with a lung phenotype and patients with group 3 PH) with similar backgrounds to our study.…”

Dual bronchodilation for the treatment of COPD: From bench to bedside

“…A Japanese real‐world study suggested that, compared with new users of tiotropium, new users of tiotropium/olodaterol had a numerically lower probability of escalating to triple therapy or experiencing moderate or severe COPD exacerbations 94 . Furthermore, data from the US HealthCore Integrated Research Database revealed that both individually and in combination, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia and escalation to triple therapy in patients with COPD compared to ICS/LABA 95 ; the combined risk was reduced regardless of baseline eosinophils or exacerbation history.…”

“…93 A Japanese real-world study suggested that, compared with new users of tiotropium, new users of tiotropium/olodaterol had a numerically lower probability of escalating to triple therapy or experiencing moderate or severe COPD exacerbations. 94 Although initial optimisation of bronchodilation is not suggested in current COPD treatment guidelines or strategies, 1,4 in our opinion it is now appropriate to consider starting treatment with a LAMA/LABA combination as soon as the diagnosis of COPD is made. 96 The goal of pharmacological therapies in the treatment of patients with COPD is to reduce symptoms as well as improve health status and exercise tolerance, and reduce the risk of exacerbations.…”