Obstructive Lung Diseases: Airways 5 |

Time to COPD Exacerbation in the TONADO Studies by Disease Severity (Global Initiative for Chronic Obstructive Lung Disease [GOLD]) and Baseline Inhaled Corticosteroid (ICS) Use FREE TO VIEW

Gary Ferguson; Eric Derom; François Maltais; Florian Voss; Carlos Tafur; Roland Buhl
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Pulmonary Research Institute of Southast Michigan, Farmington Hills, MI

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;150(4_S):879A. doi:10.1016/j.chest.2016.08.979
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM

PURPOSE: Reducing exacerbations is a key goal of COPD treatment due to their detrimental effects on lung function and health status. The Phase III, TONADO studies assessed efficacy and safety of tiotropium + olodaterol (T+O) in patients with moderate to very severe COPD. We investigated if GOLD stage and baseline ICS use are prognostic for the number of patients with, and time to first, COPD exacerbation, irrespective of treatment arm.

METHODS: TONADO 1 and 2 were replicate, 52-week, double-blind, parallel-group studies (1237.5, NCT01431274; 1237.6, NCT01431287). Patients received once-daily T+O 2.5/5 or 5/5 µg, T 2.5 or 5 µg, or O 5 µg, via the Respimat inhaler. Continuation of prescribed ICS was permitted. We analyzed time to first moderate or severe exacerbation using pooled data from the two studies.

RESULTS: Of 5162 treated patients, 2588 (50.1%), 1989 (38.5%), and 581 (11.3%) were GOLD 2, 3, and 4 at baseline, respectively. Fewer GOLD 2 patients had a moderate/severe on-study exacerbation: 584 (22.6%) compared to 688 (34.6%) GOLD 3 and 211 (36.3%) GOLD 4. The 25th percentile for time to first moderate/severe exacerbation was not reached within the 52 week study period for GOLD 2, and was 201 days for GOLD 3 and 182 days for GOLD 4 patients; hazard ratios (HRs) (95% CI) were 0.59 (0.53, 0.66) for GOLD 2 vs GOLD 3, 0.55 (0.47, 0.64) for GOLD 2 vs GOLD 4, and 0.93 (0.80, 1.09) for GOLD 3 vs GOLD 4. At baseline, 2446 patients (47.4%) used ICS and 2716 (52.6%) did not. More patients with baseline ICS use had an exacerbation compared to those without ICS: 879 (35.9%) vs 605 (22.3%), respectively. The 25th percentile for time to first moderate/severe exacerbation was 191 days with ICS and was not reached in the 52 week study in patients without ICS; HR (95% CI) 1.78 (1.61, 1.98). In patients stratified by baseline ICS use within GOLD groups, ICS use was associated with shorter time to exacerbation vs no ICS: HR 1.66 (1.41, 1.95) in GOLD 2 and 1.69 (1.47, 1.93) in GOLD 3/4.

CONCLUSIONS: In this population, unselected by exacerbation history, more severe COPD by GOLD stage and ICS use were associated with increased exacerbation risk. The association between ICS use and increased exacerbation risk is likely to represent a confounding by indication bias.

CLINICAL IMPLICATIONS: This analysis confirms separation in exacerbation risk in patients with GOLD 2 versus GOLD 3/4 lung function impairment. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion.

DISCLOSURE: Gary Ferguson: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, AstraZeneca, Pearl Therapeutics, Novartis, Forest, Sunovion, Verona, Receptos, GlaxoSmithKline, Other: Boehringer-Ingelheim, AstraZeneca, Pearl Therapeutics, Sunovion, Sunovion, Theravance, Sanofi, Forest, GlaxoSmithKline Eric Derom: Consultant fee, speaker bureau, advisory committee, etc.: Actellion, Boehringer, AstraZeneca, Cipla, Chiesi, CSL Behring, Other: GlaxoSmithKline, Boehringer François Maltais: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Novartis, Other: Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Nycomed, Novartis Florian Voss: Employee: Boehringer-Ingelheim Carlos Tafur: Employee: Boehringer-Ingelheim Roland Buhl: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, TEVA, Roche, Other: Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Roche

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