Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials

Calverley, Peter M.A.; Rabe, Klaus F.; Goehring, Udo-Michael; Kristiansen, Søren; Fabbri, Leonardo M.; Martínez, Fernando J.

doi:10.1016/s0140-6736(09)61255-1

Cited by 721 publications

(681 citation statements)

References 30 publications

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“…Adverse events mostly became evident during the first 4-12 weeks and although usually subsiding with continued treatment, these events caused an increased patient withdrawal in the roflumilast-arms. In addition, no clinically relevant cardiac toxicity was reported in none of the patients [39][40][41][42].…”

Section: Adverse Events During Long-term Pde4-inhibitionmentioning

confidence: 89%

“…Recently, the results of 4 pivotal randomized controlled trials (RCT) with roflumilast in large groups of patients with moderate to severe COPD have been published [41]. Apart from the effect on lung function, the focus of these trials was on the longer-term clinical efficacy of roflumilast based on GOLD-criteria: i.e.…”

Section: Roflumilast: Pharmacokinetics Clinical Efficacy From Phase mentioning

confidence: 99%

“…The studies reported by Calverley et al (M2-124 and M2-125, respectively) used an identical study design including chronic smokers or ex-smokers (≥20 packyears) with symptomatic, (very) severe COPD characterized by chronic cough, sputum production and exacerbations [41]. The inclusion criteria were based on a post-hoc analysis of a previous study, suggesting a decrease in exacerbations by roflumilast in this COPD-phenotype [40].…”

Section: Roflumilast: Pharmacokinetics Clinical Efficacy From Phase mentioning

confidence: 99%

“…In all 6-12 months randomized controlled trials, the most commonly roflumilast-related adverse events, reported by COPD-patients, included central adverse events (nausea, headache, insomnia), gastro-intestinal side effects (diarrhea) and (modest) weight loss [39][40][41][42]. Adverse events mostly became evident during the first 4-12 weeks and although usually subsiding with continued treatment, these events caused an increased patient withdrawal in the roflumilast-arms.…”

Section: Adverse Events During Long-term Pde4-inhibitionmentioning

confidence: 99%

“…In all 4 registration trials (M2-124/125 and M2-127/128) weight loss was reported, with a mean of 2.1 kg, mostly occurring in the first 6 months of the M2-124/125 studies [41] and with a similar mean weight loss of 2.0 and 1.8 kg, respectively, in the M2-127/128 studies [42]. The largest absolute weight loss was seen in patients with a BMI >30.…”

Section: Adverse Events During Long-term Pde4-inhibitionmentioning

confidence: 99%

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PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease

Diamant

Spina

2011

Pulmonary Pharmacology & Therapeutics

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SummaryRoflumilast is a selective once daily, oral phosphodiesterase-4 inhibitor that has recently been registered in all European Union countries as novel targeted therapy for COPD, while FDA approval for the USA market is expected in 2011. In several phase III trials in patients with moderate to (very) severe COPD and in patients with symptoms of chronic bronchitis and recurrent exacerbations, roflumilast showed sustained clinical efficacy by improving lung function and by reducing exacerbation rates. These beneficial effects have also been demonstrated when added to long-acting bronchodilators (both LABA and LAMA), underscoring the anti-inflammatory activity of roflumilast in COPD. Pooled data analysis showed overall mild to moderate, mostly self-limiting adverse events, mainly consisting of nausea, diarrhea and weight loss. In this review we discuss the results of the 4 registration studies showing promising effects of roflumilast in COPD and provide an overview of the topics that still need to be addressed. keywords: PDE4-inhibitor, roflumilast, clinical trials, chronic obstructive airways disease 3

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Section: Adverse Events During Long-term Pde4-inhibitionmentioning

confidence: 89%

Section: Roflumilast: Pharmacokinetics Clinical Efficacy From Phase mentioning

confidence: 99%

Section: Roflumilast: Pharmacokinetics Clinical Efficacy From Phase mentioning

confidence: 99%

Section: Adverse Events During Long-term Pde4-inhibitionmentioning

confidence: 99%

Section: Adverse Events During Long-term Pde4-inhibitionmentioning

confidence: 99%

See 3 more Smart Citations

PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease

Diamant

Spina

2011

Pulmonary Pharmacology & Therapeutics

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Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease

Chong¹,

Poole²,

Leung³

et al. 2011

Cochrane Database of Systematic Reviews

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Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease

Chong

Leung

Poole

2013

Cochrane Database of Systematic Reviews

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BackgroundChronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea, and a reduction in lung function, quality of life, and life expectancy. Apart from smoking cessation, no other treatments that slow lung function decline are available. Roflumilast and cilomilast are oral phosphodiesterase-4 (PDE ) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This Cochrane Review was first published in 2011, and was updated in 2017 and 2020. ObjectivesTo evaluate the e icacy and safety of oral PDE inhibitors for management of stable COPD. Search methodsWe identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 9 March 2020). We found other trials at web-based clinical trials registers. Selection criteriaWe included RCTs if they compared oral PDE inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy. Data collection and analysisWe used standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were change in lung function (minimally important di erence (MID) = 100 mL) and quality of life (scale 0 to 100; higher score indicates more limitations). Main resultsWe found 42 RCTs that met the inclusion criteria and were included in the analyses for roflumilast (28 trials with 18,046 participants) or cilomilast (14 trials with 6457 participants) or tetomilast (1 trial with 84 participants), with a duration between six weeks and one year or longer. These trials included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II to IV), with mean age of 64 years.We judged risks of selection bias, performance bias, and attrition bias as low overall amongst the 39 published and unpublished trials.

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Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials

Cited by 721 publications

References 30 publications

PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease

PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease

Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease

Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease

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