The Effect on Total Mortality of Adding Inhaled Corticosteroids to Long-Acting Bronchodilators for COPD: A Real Practice Analysis in Italy

Martino, Mirko Di; Agabiti, Nera; Cascini, Silvia; Kirchmayer, Ursula; Bauleo, Lisa; Fusco, Danilo; Belleudi, Valeria; Pinnarelli, Luigi; Voci, Claudio; Patorno, Elisabetta; Pistelli, Riccardo; Davoli, Marina

doi:10.3109/15412555.2015.1044861

Cited by 17 publications

(21 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings were confirmed in sensitivity analyses, considering users of the combination tiotropium + LABA as exposed to tiotropium and excluding patients using ICS during follow‐up. The observed but not statistically significant increase in risk for LABA with respect to LABA + ICS was previously reported for the same study population in a paper which is in press …”

Section: Discussioncontrasting

confidence: 94%

One‐year mortality associated with COPD treatment: a comparison of tiotropium and long‐acting beta2‐agonists in three Italian regions: results from the OUTPUL study

Kirchmayer¹,

Cascini²,

Agabiti³

et al. 2016

Pharmacoepidemiology and Drug

Self Cite

View full text Add to dashboard Cite

PurposeLong‐acting bronchodilators, i.e. beta‐2‐agonists (LABA) and tiotropium are commonly used in COPD treatment. Choice of a specific agent is based on effectiveness and safety. Evidence yields controversial results with respect to mortality. The present study compared one‐year mortality associated to treatment with tiotropium versus LABA.MethodsA population‐based cohort study using data from Italian health information systems was performed. Patients aged 45+ years, discharged with COPD diagnosis in 2006–2009 were identified. Through record linkage with drug claims, patients who received a first prescription of LABA or tiotropium within 6 months after discharge were enrolled. The main analysis was restricted to naïve users (no prior use of either LABA or tiotropium). We used ‘intention to treat’ (ITT) and ‘as treated’ (AT) approaches. We followed patients for a maximum of 12 months. Hazard ratios (HRs) were calculated by Cox regression including quintiles of propensity score. In sensitivity analysis patients receiving tiotropium + LABA combination were included in the tiotropium group.ResultsAmong the 33 891 enrolees, 28% were exposed to Tio, 56% to LABA, 16% to both. Overall mean age was 74 years and the mortality rate was 122/1000 person‐years (py) at the ITT analysis and 108/1000 py at the AT analysis. The adjusted HR for tiotropium only compared with LABA only was 1.06 (95%CI: 0.94–1.20) at the ITT analysis and 1.00 (95%CI: 0.93–1.08) at the AT analysis. Results were robust in sensitivity analysis.ConclusionsIn this real‐world study use of tiotropium was not associated with an increased risk of one‐year mortality compared with LABA. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

show abstract

Section: Discussioncontrasting

confidence: 94%

One‐year mortality associated with COPD treatment: a comparison of tiotropium and long‐acting beta2‐agonists in three Italian regions: results from the OUTPUL study

Kirchmayer¹,

Cascini²,

Agabiti³

et al. 2016

Pharmacoepidemiology and Drug

Self Cite

View full text Add to dashboard Cite

show abstract

“…The apparent contradiction between increased pneumonia risk and unchanged/decreased mortality led the authors to speculate that pneumonia may result from the local immunosuppressive effects of ICS, which may, however, modulate the severity of pneumonia via their anti-inflammatory effects. Two recent independent observational studies provide support for this notion 57,58…”

Section: Discussionmentioning

confidence: 85%

Fluticasone propionate/formoterol for COPD management: a randomized controlled trial

Papi¹,

Dokic²,

Tzimas³

et al. 2017

COPD

View full text Add to dashboard Cite

PurposeTo evaluate fluticasone propionate/formoterol (FP/FORM) in COPD.Patients and methodsCOPD patients with forced expiratory volume in 1 s (FEV1) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations.ResultsIn total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P=0.084). Pre- and post-dose FEV1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (P≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P=0.077). There were more St George’s Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (P≤0.066). Acute β2-agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups.ConclusionFP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments.

show abstract

“…The as‐treated approach accounts for switching therapy and therapy discontinuation during the follow‐up period. However, both switching and discontinuation might be predictors of adverse health outcomes due to drug intolerance or treatment failure, which may have led to informative censoring . To limit this potential bias, a 30‐day grace period for drug discontinuation was applied, according to previous studies .…”

Section: Discussionmentioning

confidence: 99%

“…The number of DDD was converted to the number of days the patient was treated, counting 1 DDD per day and distributing all available DDDs to days of follow‐up (including the days covered by the last prescription). At the end of the exposure period (ie, when all available DDDs were expired), a renewal time of 30 days (ie, grace time) was applied during which the patient was considered “exposed” without being censored for discontinuation . In the case of switching, a 7‐day grace time was used to limit the potential misclassification of exposure accounting for the 5‐ to 6‐day half‐life of tiotropium terminal elimination …”

Section: Methodsmentioning

confidence: 99%

Role of Tiotropium in Reducing Exacerbations of Chronic Obstructive Pulmonary Disease When Combined With Long‐Acting β₂‐Agonists and Inhaled Corticosteroids: The OUTPUL Study

Ferroni¹,

Belleudi²,

Cascini³

et al. 2016

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Combined inhaled therapy in chronic obstructive pulmonary disease (COPD) is commonly used, but its benefits remain controversial. We assessed the effect of tiotropium in reducing COPD exacerbations when combined with long‐acting β2 agonists (LABA) and/or inhaled corticosteroids (ICS). This new‐user cohort study is based on administrative data from 3 Italian regions. We identified adults hospitalized for COPD from 2006 to 2009 who were newly prescribed a fixed LABA/ICS combination (double therapy). We classified patients according to whether tiotropium was also prescribed (triple therapy), using both intention‐to‐treat and as‐treated approaches, and followed them for 1 year. COPD exacerbations were measured as outcomes. Multivariate and propensity score‐adjusted hazard ratios (HRs, 95%CI) were calculated with Cox regression models. We identified 5717 new users of LABA/ICS of which 31.9% initiated triple therapy. In the intention‐to‐treat analysis, the multivariate adjusted HR for moderate, severe, and any exacerbations were 1.02 (95%CI 0.89‐1.16), 0.92 (95%CI 0.76‐1.12), and 1.08 (95%CI 0.91‐1.28), respectively. The propensity score adjustment produced similar results. In the subcohort of patients with previous exacerbations, triple therapy was significantly associated with reduced risk of moderate exacerbations, compared to double therapy (HR 0.68, 95%CI 0.48‐0.98 in intention‐to‐treat approach). In conclusion, the addition of tiotropium to LABA/ICS did not reduce COPD exacerbations compared to LABA/ICS alone. A protective role for moderate exacerbations was found in patients at risk of frequent exacerbations. Given the impact of exacerbations on health status and prognosis, it is crucial to target COPD patients for optimal treatment.

show abstract

The Effect on Total Mortality of Adding Inhaled Corticosteroids to Long-Acting Bronchodilators for COPD: A Real Practice Analysis in Italy

Abstract: Our findings showed a beneficial effect on mortality of adding inhaled corticosteroids to long-acting bronchodilators. The advantage was much more pronounced in patients with frequent exacerbations.

Cited by 17 publications

References 41 publications

One‐year mortality associated with COPD treatment: a comparison of tiotropium and long‐acting beta2‐agonists in three Italian regions: results from the OUTPUL study

One‐year mortality associated with COPD treatment: a comparison of tiotropium and long‐acting beta2‐agonists in three Italian regions: results from the OUTPUL study

Fluticasone propionate/formoterol for COPD management: a randomized controlled trial

Role of Tiotropium in Reducing Exacerbations of Chronic Obstructive Pulmonary Disease When Combined With Long‐Acting β₂‐Agonists and Inhaled Corticosteroids: The OUTPUL Study

Contact Info

Product

Resources

About

The Effect on Total Mortality of Adding Inhaled Corticosteroids to Long-Acting Bronchodilators for COPD: A Real Practice Analysis in Italy

Abstract: Our findings showed a beneficial effect on mortality of adding inhaled corticosteroids to long-acting bronchodilators. The advantage was much more pronounced in patients with frequent exacerbations.

Cited by 17 publications

References 41 publications

One‐year mortality associated with COPD treatment: a comparison of tiotropium and long‐acting beta2‐agonists in three Italian regions: results from the OUTPUL study

One‐year mortality associated with COPD treatment: a comparison of tiotropium and long‐acting beta2‐agonists in three Italian regions: results from the OUTPUL study

Fluticasone propionate/formoterol for COPD management: a randomized controlled trial

Role of Tiotropium in Reducing Exacerbations of Chronic Obstructive Pulmonary Disease When Combined With Long‐Acting β2‐Agonists and Inhaled Corticosteroids: The OUTPUL Study

Contact Info

Product

Resources

About

Role of Tiotropium in Reducing Exacerbations of Chronic Obstructive Pulmonary Disease When Combined With Long‐Acting β₂‐Agonists and Inhaled Corticosteroids: The OUTPUL Study