17 augustus 2005: bron: Medscape en Lancet 2005;366:563-571 en J Allergy Clin Immunol. 2005 Aug;116(2):292-8

Het middel Roflumilast - een zogeheten phosphodiesterase-4 remmer en dus geen steroïd en dagelijks via een tabletje in te nemen - verbetert significant de longfunctie van COPD patiënten (chronic obstructive pulmonary disease), blijkt uit een Nederlands-Duits garandomiseerde placebo gecontroleerde fase III studie bij totaal 1411 COPD patiënten door het tegengaan van chronische ontstekingen. Het Nederlandse ziekenhuis dat hieraan meewerkte is het LUMC - Leiden. Onder de studie abstracten van Rofluminast bij de COPD patiënten staat het abstract van een kleinschalige maar wel gerandomiseerde studie die lijkt te bewijzen dat Rofluminast ook bij astma patiënten - astma gaat immers ook gepaard met chronische ontstekingen - een bruikbaar medicijn kan worden. Hier zo goed als letterlijk vertaald de resultaten van deze studie, die o.i. ook belangrijk kan zijn voor longkankerpatiënten, maar vraag nadrukkelijk uw arts advies hierover.

RESULTATEN: 1157 (82%) patiënten completeerden de studie; 32 (11%) verliet voortijdig de placebo groep, 100 (17%) verliet voortijdig de roflumilast 250 microg groep, en 124 (22%) verliet de roflumilast 500 microg groep. Postbronchodilator FEV1 aan het eind van de behandeling verbeterde significant met roflumilast 250 microg (door 74 mL [SD 18]) en roflumilast 500 microg (door 97 mL ) vergeleken met placebo (p<0.0001). Verbetering in gezondheid gerelateerde kwaliteit van leven was hoger met roflumilast 250 microg (-3.4 units [0.6]) en roflumilast 500 microg (-3.5 units [0.6]) dan met placebo (-1.8 units [0.8]), alhoewel de verschillen tussen de behandelgroepen niet significant waren. De mediane aantallen van verslechtering per patiënt waren 1.13 (2.37), 1.03 (2.33), en 0.75 (1.89) met respectievelijk placebo, roflumilast 250 microg, en roflumilast 500 microg. Ernstigste bijwerkingen waren mild tot gemiddeld in intensiteit en konden worden opgelost tijdens de studieduur.

INTERPRETATIE: Roflumilast is een beloftevolle kandidaat voor een anti-ontstekings behandeling van COPD omdat het de longfucntie verbeterde en verslechtering verminderde in vergelijking met placebo. Lange termijn studies zijn nodig om het volledige effect op gezondheid gerelateerde kwaliteit van leven te meten.

Lancet. 2005 Aug 13-19;366(9485):563-71.

Roflumilast--an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial.

Rabe KF, Bateman ED, O'Donnell D, Witte S, Bredenbroker D, Bethke TD. Leiden University Medical Centre, Leiden, Netherlands. k.f.rabe@lumc.nl

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation associated with chronic inflammation. There are few treatment options for the disease. This study assessed the efficacy and safety of roflumilast, a phosphodiesterase-4 inhibitor, in patients with moderate to severe COPD.

METHODS: This phase III, multicentre, double-blind, randomised, placebo-controlled study was undertaken in an outpatient setting. 1411 patients with COPD were randomly assigned roflumilast 250 microg (n=576), roflumilast 500 microg (n=555), or placebo (n=280) given orally once daily for 24 weeks. Primary outcomes were postbronchodilator FEV1 and health-related quality of life. Secondary outcomes included other lung function parameters and COPD exacerbations. Analyses were by intention to treat.

FINDINGS: 1157 (82%) patients completed the study; 32 (11%) withdrew from the placebo group, 100 (17%) from the roflumilast 250 microg group, and 124 (22%) from the roflumilast 500 microg group. Postbronchodilator FEV1 at the end of treatment significantly improved with roflumilast 250 microg (by 74 mL [SD 18]) and roflumilast 500 microg (by 97 mL ) compared with placebo (p<0.0001). Improvement in health-related quality of life was greater with roflumilast 250 microg (-3.4 units [0.6]) and roflumilast 500 microg (-3.5 units [0.6]) than with placebo (-1.8 units [0.8]), although the differences between treatment groups were not significant. The mean numbers of exacerbations per patient were 1.13 (2.37), 1.03 (2.33), and 0.75 (1.89) with placebo, roflumilast 250 microg, and roflumilast 500 microg, respectively. Most adverse events were mild to moderate in intensity and resolved during the study.

INTERPRETATION: Roflumilast is a promising candidate for anti-inflammatory COPD treatment because it improved lung function and reduced exacerbations compared with placebo. Long-term studies are needed to fully assess the effect on health-related quality of life.

PMID: 16099292 [PubMed - in process]

Bron: Medascape:

Roflumilast Improves Lung Function in COPD Patients

NEW YORK (Reuters Health) Aug 11 - Treatment with roflumilast, a phosphodiesterase-4 inhibitor, can improve lung function and reduce flare-ups in patients with moderate to severe COPD, according to a report in the August 13th issue of The Lancet. Chronic inflammation is known to play a key role in COPD, but corticosteroids appear to have little effect on the disease process, Dr. Klaus F. Rabe, from Leiden University Medical Centre in the Netherlands, and colleagues note. Thus, there has been a search for anti-inflammatory agents with efficacy against COPD. Recently, the focus has been on phosphodiesterase-4 inhibitors. In the current phase III study, Dr. Rabe's team assessed the outcomes of 1411 COPD patients who were randomly assigned in an outpatient setting to receive roflumilast, at one of two doses (250 or 500 micrograms), or placebo once daily for 24 weeks. At either dose, roflumilast was associated with significant improvements in postbronchodilator FEV1 compared with placebo, the investigators note (p < 0.0001). Similarly, both doses provided significantly greater improvements in health-related quality of life than did placebo. The percentage of patients with exacerbations was about 36% in the low-dose roflumilast and placebo groups, whereas the percentage in the high-dose roflumilast group was significantly lower, at 28% (p = 0.0114). Adverse effects in the roflumilast groups were generally mild to moderate in severity and occurred with comparable frequency as in the placebo group. However, diarrhea and nausea were more common in the roflumilast groups than among controls. "The phosphodiesterase-4 inhibitor class shows promise as a new therapeutic strategy for patients with COPD," the authors conclude. The study was funded by German drug company ALTANA Pharma Ag, which is developing roflumilast. Lancet 2005;366:563-571.
,br> J Allergy Clin Immunol. 2005 Aug;116(2):292-8.

Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions.

van Schalkwyk E, Strydom K, Williams Z, Venter L, Leichtl S, Schmid-Wirlitsch C, Bredenbroker D, Bardin PG.

From the Department of Internal Medicine, University of Stellenbosch, Cape Town.

BACKGROUND: Asthma is a chronic inflammatory disease with increasing incidence worldwide. Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 that prevents the breakdown of cyclic adenosine monophosphate levels, leading to inhibition of proinflammatory signaling.

OBJECTIVE: The objective of this study was to investigate the effects of repeated doses of 250 or 500 mug of roflumilast on asthmatic airway responses to allergen.

METHODS: Twenty-three patients with mild asthma with an FEV(1) of 70% of predicted value or greater were enrolled in a randomized, double-blind, placebo-controlled, 3-period crossover study. Patients participated in 3 treatment periods (7-10 days) separated by washout periods (2-5 weeks). Patients received 250 mug of oral roflumilast, 500 mug of roflumilast, or placebo once daily. Allergen challenge was performed at the end of each treatment period, followed by FEV(1) measurements over the ensuing 24 hours.

RESULTS: Late asthmatic reactions (LARs) were reduced by 27% (P=.0110) and 43% (P=.0009) in patients treated with 250 and 500 mug of roflumilast, respectively, versus placebo. Roflumilast, 250 and 500 mug, also attenuated early asthmatic reactions by 25% (P=.0038) and 28% (P=.0046), although not to the same extent as LAR attenuation. Roflumilast was well tolerated. No serious adverse events or discontinuations caused by adverse events were reported.

CONCLUSION: Once-daily oral roflumilast modestly attenuated early asthmatic reactions and, to a greater extent, LARs to allergen in patients with mild allergic asthma. Pronounced suppression of late responses in an allergen challenge model suggests that roflumilast might have anti-inflammatory activity, which could provide clinical efficacy in chronic inflammatory pulmonary diseases, such as asthma. PMID: 16083782 [PubMed - in process]


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