ArticleRespiratory research2011
Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD.
Article in Respiratory research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 117 papers, 11 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Roflumilast on Exacerbation Rate in Patients With Chronic Obstructive Pulmonary Disease. A 52-week, Multicenter, Double-blind Study With 500 mcg Roflumilast Once Daily Versus Placebo.
Effect of Roflumilast on Exacerbation Rate in Patients With Chronic Obstructive Pulmonary Disease. A 52 Weeks Double Blind Study With 500mcg Roflumilast Once Daily Versus Placebo. Ratio-Study.
Who cites it
117 citing papers in PubMed, 11 syntheses or guidelines pooled it, 280 citations in OpenAlex.
- A comprehensive systematic review and meta-analysis of ensifentrine in COPD: dose-dependent effects, safety profile, and GRADE-based certainty of evidence.Naunyn-Schmiedeberg's archives of pharmacology · 2026Pooled it
- Effects of Roflumilast on Patients with Chronic Obstructive Pulmonary Disease Treated with Inhaled Corticosteroid/Long-ActingComputational and mathematical methods in medicine · 2022Pooled it
- Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease.The Cochrane database of systematic reviews · 2020Pooled it
- Mepolizumab in the treatment of eosinophilic chronic obstructive pulmonary disease.International journal of chronic obstructive pulmonary disease · 2019Pooled it
- Effect of roflumilast on chronic obstructive pulmonary disease: a systematic review and meta-analysis.Irish journal of medical science · 2018Pooled it
- Pharmacological mechanism of roflumilast in the treatment of asthma-COPD overlap.Drug design, development and therapy · 2018Pooled it
- Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease.The Cochrane database of systematic reviews · 2017Pooled it
- Effects of yoga in adults with type 2 diabetes mellitus: A meta-analysis.Journal of diabetes investigation · 2017Pooled it
- Can roflumilast, a phosphodiesterase-4 inhibitor, improve clinical outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease? A meta-analysis.Respiratory research · 2016Pooled it
- Potential treatment benefits and safety of roflumilast in COPD: a systematic review and meta-analysis.International journal of chronic obstructive pulmonary disease · 2016Pooled it
- [Spanish COPD Guidelines (GesEPOC): Pharmacological treatment of stable COPD].Atencion primaria · 2012Guideline
- Effect of chronic mucus hypersecretion on treatment responses to inhaled therapies in patients with chronic obstructive pulmonary disease: Post hoc analysis of the IMPACT trial.Respirology (Carlton, Vic.) · 2022Trial
- Efficacy and safety of CHF6001, a novel inhaled PDE4 inhibitor in COPD: the PIONEER study.Respiratory research · 2020Trial
- Sputum and blood transcriptomics characterisation of the inhaled PDE4 inhibitor CHF6001 on top of triple therapy in patients with chronic bronchitis.Respiratory research · 2020Trial
- Adherence to roflumilast under dose-escalation strategy in Korean patients with COPD.International journal of chronic obstructive pulmonary disease · 2019Trial
- The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD.The European respiratory journal · 2018Trial
- The development of AZD7624 for prevention of exacerbations in COPD: a randomized controlled trial.International journal of chronic obstructive pulmonary disease · 2018Trial
- A randomised, placebo-controlled trial of anti-interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease.Respiratory research · 2017Trial
- Efficacy and Safety of Roflumilast in Korean Patients with COPD.Yonsei medical journal · 2016Trial
- Effects of roflumilast in COPD patients receiving inhaled corticosteroid/long-acting β2-agonist fixed-dose combination: RE(2)SPOND rationale and study design.International journal of chronic obstructive pulmonary disease · 2016Trial
57 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive. This led to the question of whether a responsive subset existed that could be investigated further.
methodsThe datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.
resultsThe pooled analysis included 2686 randomized patients. Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026). Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014). The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).
conclusionsThis post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS. These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment. TRIALS REGISTRATION: ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729.
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.