Intervention Review

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Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease

  1. Jimmy Chong1,
  2. Bonnie Leung1,
  3. Phillippa Poole2,*

Editorial Group: Cochrane Airways Group

Published Online: 4 NOV 2013

Assessed as up-to-date: 6 JUN 2013

DOI: 10.1002/14651858.CD002309.pub4


How to Cite

Chong J, Leung B, Poole P. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD002309. DOI: 10.1002/14651858.CD002309.pub4.

Author Information

  1. 1

    Tauranga Hospital, Tauranga, New Zealand

  2. 2

    University of Auckland, Department of Medicine, Auckland, New Zealand

*Phillippa Poole, Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand. p.poole@auckland.ac.nz.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 4 NOV 2013

SEARCH

References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Cilomilast 039 {published data only}
  • Edelson JD, Compton C, Nieman R, Robinson CB, Amit O, Bagchi I, et al. Cilomilast (Ariflo) a potent selective phosphodiesterase 4 inhibitor, reduces exacerbations in COPD patients: Results of a 6 month trial. American Journal of Respiratory and Critical Care Medicine 2001;163(5 Suppl):A771.
  • Edelson JD, Compton C, Nieman R, Robinson CB, Watt R, Amit O, et al. Cilomilast (Ariflo) improves health status in patients with COPD: Results of a 6-month trial. American Journal of Respiratory and Critical Care Medicine 2001;163(5 Suppl):A277.
  • GSK CTR-039. A randomized, 24-week, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety and tolerability of cilomilast (15 mg twice daily) in patients with chronic obstructive pulmonary disease (207499/039). http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=207499%2f039&studyId=42B8787E-719D-4A66-8180-A7643F656A2A&compound=cilomilast (accessed 25 May 2010).
  • Rennard SI, Schachter N, Strek M, Rickard K, Amit O. Cilomilast for COPD: Results of a 6-month, placebo controlled study of a potent, selective inhibitor of phosphodiesterase 4. Chest 2006;129(1):55-66.
Cilomilast 042 {unpublished data only}
  • GSK CTR-042. A randomized, 24-week, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety and tolerability of cilomilast (15 mg twice daily) in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24046.pdf (accessed 25 May 2010).
Cilomilast 076 {published and unpublished data}
  • GSK CTR-076. A 12-week, multicentre, double-blind, placebo-controlled, parallel-group study to evaluate the anti-inflammatory activity of SB207499 15 mg twice daily in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24047.pdf (accessed 25 May 2010).
  • Gamble E, Grootendorst DC, Brightling CE, Troy S, Qiu Y, Zhu J, et al. Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 2003;168:976-82.
Cilomilast 091 {unpublished data only}
  • GSK CTR-091. A randomized, 24-week, double-blind, placebo-controlled, parallel-group study followed by a 2-week, randomized, double-blind, run-out phase to evaluate the efficacy, safety, tolerability and discontinuation of SB207499 (15 mg twice daily) in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24048.pdf (accessed 25 May 2010).
Cilomilast 103657 {unpublished data only}
  • GSK CTR-657. A randomized, 24-week, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety and tolerability of cilomilast (15 mg BID) in patients with Chronic Obstructive Pulmonary Disease (COPD). http://www.gsk-clinicalstudyregister.com/files/pdf/20593.pdf (accessed 25 May 10).
Cilomilast 110 {unpublished data only}
  • GSK CTR-110. A 12-week, multicenter, double-blind, placebo-controlled, parallel-group study to evaluate the anti-inflammatory activity of cilomilast 15 mg twice daily in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24049.pdf (accessed 25 May 2010).
Cilomilast 111 {published and unpublished data}
  • GSK CTR-111. A 12-week, randomized, double-blind, placebo-controlled, parallel-group study to investigate the effect of cilomilast (15 mg twice daily) on trapped gas volume in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24050.pdf (accessed 25 May 2010).
  • Zamel N, McClean P, Zhu J, Schryver B, Madan A, Robinson CB, et al. Effect of cilomilast (Ariflo) on trapped gas volume and indices of hyperinflation in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):A226.
Cilomilast 121 {unpublished data only}
  • GSK CTR-121. A randomized, 24-week, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety and tolerability of cilomilast (15 mg BID) in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24042.pdf (accessed 25 May 2010).
Cilomilast 156 {unpublished data only}
  • GSK CTR-156. A randomized, 24-week, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety and tolerability of cilomilast (15 mg BID) in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24051.pdf (accessed 25 May 2010).
Cilomilast 157 {unpublished data only}
  • GSK CTR-157. A randomised, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety and tolerability of oral cilomilast (15 mg bd) when given as maintenance treatment for 12 months to subjects with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24053.pdf (accessed 25 May 2010).
Cilomilast 168 {published and unpublished data}
  • GSK CTR-168. A randomized, 12-week, double-blind, placebo-controlled, parallel-group study to evaluate the safety and tolerability of cilomilast 15 mg twice daily in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24054.pdf (accessed 25 May 2010).
  • Reisner C, Zhu J, Morris A, Lim J, Knobil K. Assessment of cardiac events via 24-hour electrocardiographic (Holter) monitoring with cilomilast in chronic obstructive pulmonary disease [Abstract]. American Thoracic Society 99th International Conference; 2003 May 16-21; Seattle. 2003:Poster D86, A035.
  • Reisner C, Zhu J, Morris A, Lim J, Knobil K. Assessment of cardiac events via 24-hour electrocardiographic (Holter) monitoring with cilomilast in chronic obstructive pulmonary disease. European Respiratory Journal 2003;22(Suppl 45):Abstract No: P522.
Cilomilast 180 {unpublished data only}
  • GSK CTR-180. An 18-week randomized, double-blind, placebo-controlled, multicenter study designed to compare treatment with cilomilast to that with placebo for changes in ventilatory mechanics and function (both at rest and during exercise), as well as related exertional dyspnea and exercise performance, in hyperinflated patients with stable COPD. http://www.gsk-clinicalstudyregister.com/files/pdf/24052.pdf (accessed 25 May 2010).
Cilomilast 181 {unpublished data only}
  • GSK CTR-181. A 13-week randomised, double-blind, parallel group, multicentre study to compare the bronchial anti-inflammatory activity of oral cilomilast (15 mg bd) with placebo twice daily in subjects with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24055.pdf (accessed 25 May 10).
Compton 2001 {published and unpublished data}
  • Compton CH, Gubb J, Cedar E, Bakst A, Nieman RB, Amit O, et al. SB 207499, a second generation, oral PDE4 inhibitor, improves health status in patients with COPD. European Respiratory Society Annual Congress; 1999; Spain. 1999:P2237.
  • Compton CH, Gubb J, Nieman R, Edelson J, Amit O, Bakst A, et al. Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study. Lancet 2001;358(9278):265-70.
COPD safety pool {published data only}
  • Durmowicz AG. Cross discipline team leader review [Application number 022522Orig1s000]. Centre for drug evaluation and research (submitted 15 July 2009).
Roflumilast FK1 101 {published and unpublished data}
  • Bredenbroker D, Syed J, Leichtl S, Rathgeb F, Wurst W. Roflumilast, a new, orally active phosphodiesterase 4 inhibitor, is effective in the treatment of chronic obstructive pulmonary disease [Abstract]. European Respiratory Society Annual Congress; 2002 14-18 Sep; Stockholm. 2002:Abstract no: 2330.
  • Bredenbroker D, Syed J, Leichtl S, Rathgeb F, Wurst W. Safety of once-daily roflumilast, a new, orally active, selective phosphodiesterase 4 inhibitor, in patients with COPD. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):A595.
  • Leichtl S, Syed J, Bredenbroker D, Rathgeb F, Wurst W. Roflumilast, a new, orally active, selective phosphodiesterase 4 inhibitor, is safe and well tolerated in patients with chronic obstructive pulmonary disease [Abstract]. European Respiratory Society Annual Congress; 2002 Sep 14-17; Stockholm. 2002:Abstract no: P1907.
  • Leichtl S, Syed J, Bredenbröker D, Rathgeb F, Wurst W. Efficacy of once-daily roflumilast, a new, orally active, selective phosphodiesterase 4 inhibitor, in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):A229.
Roflumilast FK1 103 {published and unpublished data}
  • Boszormenyi-Nagy G, Pieters WR, Steffen H, Timar M, Vinkler I, Teichmann P, et al. The effect of roflumilast treatment and subsequent withdrawal in patients with COPD. American Thoracic Society International Conference; 2005 May 20-25; San Diego. 2005; Vol. B93:Poster 323.
  • Rabe K, Similowski T, Bredenbröker D, Teichmann P, Böszörményi-Nagy G. Onset of action and effect of withdrawal of roflumilast in COPD [Abstract]. European Respiratory Society Annual Congress; 2011 Sep 24-28; Amsterdam. 2011; Vol. 38, issue 55:147s [P863].
Roflumilast IN-108 {unpublished data only}
  • Ping J. Clinical pharmacology and biopharmaceutics review(s) [Application number 022522Orig1s000]. Centre for drug evaluation and research. (submitted 21 December 2010).
Roflumilast JP-706 {unpublished data only}
  • Ping J. Clinical pharmacology and biopharmaceutics review(s) [Application number 022522Orig1s000]. Centre for drug evaluation and research. (submitted 21 December 2010).
Roflumilast M2-107 {published and unpublished data}
  • Bateman ED, Holmes M, Muir JF, Andrae K, Witte S, Bredenbroeker D. Safety profile of roflumilast, a novel, selective phosphodiesterase 4 inhibitor, in patients with moderate to severe COPD [Abstract]. American Thoracic Society 100th International Conference; 2004 May 21-26; Orlando. 2004:C43;Poster F17.
  • O'Donnell D, Muir JF, Jenkins C, Plit P, Brockhaus F, Witte S, et al. Roflumilast, a novel selective phosphodiesterase 4 inhibitor, improves quality of life and lowers exacerbation rate in patients with moderate to severe COPD [Abstract]. American Thoracic Society 100th International Conference; 2004 May 21-26; Orlando. 2004 Orlando:C44;Poster J58.
  • Rabe F, O'Donnell D, Muir F, Jenkins C, Witte S, Bredenbroeker D, et al. Roflumilast an oral once daily PDE4 inhibitor improves lung function and reduces exacerbation rates in patients with COPD [Abstract]. European Respiratory Journal 2004;24(Suppl 48):21s.
  • Rabe KF, Bateman ED, O'Donnell D, Witte S, Bredenbröker D, Bethke TD. Roflumilast - an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2005;36(9485):563-71.
  • Rabe KF, Chapman KR, Joubert J, Vetter N, Witte S, Bredenboecker D. Roflumilast, a novel, selective phosphodiesterase 4 inhibitor, improves lung function in patients with moderate to severe COPD [Abstract]. American Thoracic Society 100th International Conference; 2004 May 21-26; Orlando. 2004:C22;Poster 509.
  • Rabe KF, O'Donnell D, Bateman ED, Andrae K, Witte S, Bredenbroeker D. Roflumilast improves lung function and quality of life in chronic obstructive pulmonary disease [Abstract]. Chest 2004;126(4 Suppl):709S-a.
Roflumilast M2-110 {unpublished data only}
  • Effect of Roflumilast on Pulmonary Function and Respiratory Symptoms in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BY217/M2-110). http://clinicaltrials.gov/ct2/show/study/NCT00062582 (accessed 6 June 2013).
Roflumilast M2-111 {published data only}
  • Rennard SI, Calverley PM, Goehring UM, Bredenbroker D, Martinez FJ. Reduction of exacerbations by the PDE4 inhibitor roflumilast-the importance of defining different subsets of patients with COPD. Respiratory Research 2011;12:18. [1465-993X: (Electronic). 1465-9921 (Linking)]
  • Rusch H, Gooss A, Bethke TD, Rennard S. Efficacy of roflumilast when used with concomitant inhaled corticosteroids from the OPUS/RATIO studies [Abstracts]. Respiration 2011;82(1):67-107.
Roflumilast M2-111+M2-112 {published data only}
  • Rennard SI, Calverley PM, Goehring UM, Bredenbroker D, Martinez FJ. Reduction of exacerbations by the PDE4 inhibitor roflumilast-the importance of defining different subsets of patients with COPD. Respiratory Research 2011; Vol. 12:18. [1465-993X: (Electronic). 1465-9921 (Linking)]
  • Rusch H, Gooss A, Bethke TD, Rennard S. Efficacy of roflumilast when used with concomitant inhaled corticosteroids from the OPUS/RATIO studies [Abstracts]. Respiration 2011;82(1):67-107.
Roflumilast M2-112 {published and unpublished data}
  • Calverley PM, Fabbri LM, Teichmann P, Bredenbroeker D. Effect of roflumilast on lung function and exacerbations in patients with chronic obstructive pulmonary disease: results of a one year study [Abstract]. Thorax 2005;2(Suppl II):ii42.
  • Calverley PM, Sanchez-Toril F, McIvor A, Teichmann P, Bredenbroeker D, Fabbri LM. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 2007;176(2):154-61.
  • Calverley PM, Sanchez-Toril F, McIvor RA, Teichmann P, Bredenbroeker D, Fabbri LM. Effect of roflumilast on lung function: a 1-year study in patients with severe to very severe COPD [Abstract]. Proceedings of the American Thoracic Society; 2006 May 19-24; San Diego. 2006:A725.
  • Fabbri LM, Sanchez-Toril F, McIvor RA, Teichmann P, Bredenbroeker D, Calverley PM. Effect of roflumilast on exacerbations: a 1-year study in patients with severe to very severe COPD [Abstract]. American Thoracic Society Conference; 2006 May 19-24; San Diego. 2006:A841;Poster 615.
  • Mclvor RA, Calverley PM, Sanchez-Toril F, Teichmann P, Bredenbroeker D, Fabbri LM. Effect of roflumilast on quality of life: a 1-year study in patients with severe to very severe COPD. American Thoracic Society Conference; 2006 May 19-24; San Diego. 2006; Vol. 3:A850.
  • Rennard SI, Calverley PM, Goehring UM, Bredenbroker D, Martinez FJ. Reduction of exacerbations by the PDE4 inhibitor roflumilast-the importance of defining different subsets of patients with COPD. Respiratory Research 2011;12:18. [1465-993X: (Electronic). 1465-9921 (Linking)]
  • Rusch H, Gooss A, Bethke TD, Rennard S. Efficacy of roflumilast when used with concomitant inhaled corticosteroids from the OPUS/RATIO studies [Abstracts]. Respiration 2011;82(1):67-107.
  • Rutten-van Molken M, Van Nooten F, Lindermann M, Caser M. The 1-year cost effectiveness of roflumilast for the treatment of severe to very severe COPD patients [Abstract]. European Respiratory Journal 2007;30(Suppl 51):194s, P1188.
Roflumilast M2-118 {published data only}
  • O'Donnell DE, Bredenbroker D, Brose M, Webb KA. Physiological effects of roflumilast at rest and during exercise in COPD. European Respiratory Journal 2012;39(5):1104-12. [ES:1399-3003: IL:0903-1936]
Roflumilast M2-119 {published data only}
  • Hui D, Mahayiddin A, Roa C, Kwa KH, Bredenbröker D, Goehring UM, et al. Roflumilast in Asian patients with COPD: A randomised placebo-controlled trial [Abstract]. European Respiratory Society Annual Congress; 2011 Sep 24-28; Amsterdam. 2011; Vol. 38, issue 55:600s [P3364].
  • Lee SD, Hui DS, Mahayiddin AA, Roa CC, Kwa KH, Goehring UM, et al. Roflumilast in Asian patients with COPD: A randomized placebo-controlled trial. Respirology (Carlton, Vic.) 2011;16(8):1249-57.
Roflumilast M2-121 {unpublished data only}
  • The HERO-study: Effects of Roflumilast in Patients With COPD (Chronic Obstructive Pulmonary Disease) (BY217/M2-121). http://clinicaltrials.gov/ct2/show/NCT00108823?term=roflumilast+copd&rank=21 (accessed 6 June 2013).
Roflumilast M2-124 {published and unpublished data}
  • Calverley PM, Rabe KF, Goehring U-M, Kristiansen S, Fabbri LM, Martinez FJ, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009;374(9691):685-94.
  • Martinez F, Hanania N, AURA Study Team. Efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast in patients with symptomatic chronic obstructive pulmonary disease in the M2-124 study. Chest 2009;136(4):3S-e.
  • Nowak D, Ehlken B, Kotchie R, Wecht S, Magnussen H. Roflumilast in combination with long-acting bronchodilators. Deutsche Medizinische Wochenschrift 2013;138(4):119-25.
Roflumilast M2-124+M2-125 {published data only}
  • Bateman ED, Rabe KF, Calverley PMA, Goehring UM, Brosee M, Bredenbroker D, et al. Roflumilast with long-acting beta2-agonists for COPD: Influence of exacerbation history. European Respiratory Journal 2011;38(3):553-60.
  • Calverley P, Fabbri L, Rabe K, Goehring UM, Martinez F. Efficacy of the PDE4 inhibitor roflumilast in COPD patients with chronic bronchitis [Abstract]. European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna. 2009:1629.
  • Calverley P, Martinez F, Goehring UM, Bredenbröker D, Brose M, Vogelmeier C. Impact of roflumilast treatment on the rate and duration of exacerbations and overall steroid load in patients with COPD [Abstract]. European Respiratory Society Annual Congress; 2011 Sep 24-28; Amsterdam. 2011; Vol. 38, issue 55:19s [P248].
  • Calverley PM, Rabe KF, Goehring U-M, Kristiansen S, Fabbri LM, Martinez FJ, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009;374(9691):685-94.
  • Calverley PMA, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ. Erratum: Roflumilast in symptomatic chronic obstructive pulmonary disease: Two randomised clinical trials (The Lancet (2009) 374 (685-694)). Lancet 2010;376(9747):1146.
  • Gooss A, Rusch H, Bethke TD, Hanania N. Efficacy of roflumilast in patients receiving concomitant treatments for chronic obstructive pulmonary disease over 12 months [Abstract]. Respiration 2011;82(1):67-107.
  • Hanania NA, Brose M, Larsson T, Rabe KF. Efficacy of roflumilast in patients receiving concomitant treatments for chronic obstructive pulmonary disease over 12 months [Abstract]. American Journal of Respiratory and Critical Care Medicine 2010;181(Meeting Abstracts):A4435.
  • Kaplan A, Calverley P. Efficacy of roflumilast in patients with symptomatic chronic obstructive pulmonary disease (COPD) receiving concomitant bronchodilator treatments [Abstract]. Primary Care Respiratory Journal 2010;19(2):A13 [50].
  • Martinez F, Fabbri L, Rabe K, Goehring U-M, Calverley P. Safety of the PDE4 inhibitor roflumilast in COPD patients with chronic bronchitis [Abstract]. European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna. 2009:1630.
  • Nowak D, Ehlken B, Kotchie R, Wecht S, Magnussen H. Roflumilast in combination with long-acting bronchodilators. Deutsche Medizinische Wochenschrift 2013;138(4):119-25.
Roflumilast M2-125 {published data only}
  • Andrew M, Fernando J, HERMES Study Team. Efficacy and safety of the phosphodiesterase 4 inhibitor roflumilast in patients with symptomatic chronic obstructive pulmonary disease in the M2-125 study. Chest 2009;136(4):93S-b,94.
  • Calverley PM, Rabe KF, Goehring U-M, Kristiansen S, Fabbri LM, Martinez FJ, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009;374(9691):685-94.
  • Nowak D, Ehlken B, Kotchie R, Wecht S, Magnussen H. Roflumilast in combination with long-acting bronchodilators. Deutsche Medizinische Wochenschrift 2013;138(4):119-25.
Roflumilast M2-127 {published data only}
  • Chapman KR, McIvor A, Maltais F, EOS Study Team. Additional clinical benefit in patients with chronic obstructive pulmonary disease treated with roflumilast and salmeterol. Chest 2009;136(4):3S-f.
  • Chapman KR, Rabe KF. Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease (COPD) concomitantly treated with tiotropium or salmeterol [Abstract]. Primary Care Respiratory Journal 2010;19(2):A12 [44].
  • Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with long acting bronchodilators: two randomised clinical trials. Lancet 2009;374(9691):695-703.
  • Izquierdo JL, MacNee W, Biermann E, Goehring U-M, McIvor A. The PDE4 inhibitor roflumilast provides additional clinical benefit in COPD patients receiving salmeterol [Abstract]. European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna. 2009:1627.
  • Martinez F, McIvor A, Brose M, Larsson T, Goehring UM. Benefit of roflumilast therapy added to salmeterol in patients with varying chronic obstructive pulmonary disease severity [Abstract]. Chest 2010;138(4):467A.
  • Sun S, Rennard S, Calverley P, Tourkodimitris S, Rowe P, Creanga D, et al. Effect of roflumilast treatment on dyspnea in patients with chronic obstructive pulmonary disease [Abstract]. Journal of Hospital Medicine 2012;7(Suppl 2):S85-6.
  • Sun S, Rennard S, Calverley P, Tourkodimitris S, Rowe P, Creanga D, et al. Effect of roflumilast treatment on health related quality of life in patients with chronic obstructive pulmonary disease [Abstract]. Journal of Hospital Medicine 2012;7(Suppl 2):S81-2.
Roflumilast M2-128 {published data only}
  • Chapman KR, Rabe KF. Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease (COPD) concomitantly treated with tiotropium or salmeterol [Abstract]. Primary Care Respiratory Journal 2010;19(2):A12 [44].
  • Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with long acting bronchodilators: two randomised clinical trials. Lancet 2009;374(9691):695-703.
  • Paggiaro P, Foden A. Improvements in breathlessness in patients with chronic obstructive pulmonary disease treated with roflumilast and tiotropium. Chest 2009;136(4):3S-g,4.
  • Rabe K, Paggiaro P, Bernabeu L, Brose M, Geohring U-M, Fabbri L. Roflumilast, a PDE4 inhibitor, improves lung function in patients with COPD treated with tiotropium [Abstract]. European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna. 2009:1628.
  • Rennard SI, Sun S, Tourkodimitris S, Creanga D, Goehring UM, Bredenbroeker D. Effect of roflumilast treatment added to tiotropium on dyspnea in patients with chronic obstructive pulmonary disease [Abstract]. American Journal of Respiratory and Critical Care Medicine 2012;185(Meeting Abstracts):A2261.
  • Wouters EFM, Teichmann P, Brose M, Rabe KF, Fabbri LM. Effects of roflumilast, a phosphodiesterase 4 inhibitor, on body composition in chronic obstructive pulmonary disease [Abstract]. American Journal of Respiratory and Critical Care Medicine 2010;181(Meeting Abstracts):A4473.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Borker 2003 {published data only}
  • Borker RD, Morris A, Lim J, Zhu J, Reisner C. Effect of cilomilast on quality of life improvement/deterioration and non-drug costs in patients with chronic obstructive pulmonary disease. Chest 2003;124(4):170S-b,171.
Ferguson 2003 {published data only}
  • Ferguson G, Fischer TL, Morris A, Zhu J, Barnhart F, Reisner C. Cardiovascular safety of cilomilast in patients with chronic obstructive pulmonary disease. Chest 2003;124(4):171S.
Fischer 2003 {published data only}
  • Fischer T, Borker R, Barnhart F, Morris A, Zhu J. Effect of cilomilast on chronic obstructive pulmonary disease patients with impaired quality of life. Chest 2003;124(4):129S.
Grootendorst 2001 {published data only}
  • Grootendorst DC, Gauw SA, Kelly J, Murdoch RD, Sterk PJ, Rabe KF. First dose bronchodilating effect of phosphodiesterase- 4 (PDE-4) inhibition by cilomilast (Ariflo) with or without co-administration of salbutamol and/or ipratropium in COPD patients. European Respiratory Journal 2001;18(Suppl 33):1:35s.
Grootendorst 2002 {published data only}
  • Grootendorst DC, Gauw SA, Verhoosel R, van der Veen H, van der Linden A, Moesker H, et al. Effect of a PDE4 inhibitor (Bay 19-8004) on FEV1 and airway inflammation in patients with COPD. American Journal of Respiratory and Critical Care Medicine 2002;165(8 Suppl):A226.
Grootendorst 2003 {published data only}
  • Grootendorst DC, Gauw SA, Baan R, Kelly J, Murdoch RD, Sterk PJ, et al. Does a single dose of the phosphodiesterase 4 inhibitor, cilomilast (15mg), induce bronchodilation in patients with chronic obstructive pulmonary disease?. Pulmonary Pharmacology and Therapeutics 2003;16(2):115-20.
Grootendorst 2007 {published data only}
  • Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbröker D, et al. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax 2007;62(12):1081-7.
GSK256066 {published data only}
  • Lazaar AL, Mistry S, Barrett C, Lulic-Burns Z. A four-week randomized study of the safety and tolerability of the inhaled PDE4 inhibitor GSK256066 in COPD [Abstract]. American Journal of Respiratory and Critical Care Medicine 2010;181(Meeting Abstracts):A4444.
Kelsen 2002 {published data only}
  • Kelsen SG, Rennard SI, Chodosh S, Schryver B, Vleisides C, Zhu J. COPD exacerbation in a 6-month trial of cilomilast (Ariflo) a potent, selective phosphodiesterase 4 inhibitor. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):A271.
Knobil 2003 {published data only}
  • Knobil K, Morris A, Zhu J, Fischer T, Reisner C. Cilomilast is efficacious in chronic obstructive pulmonary disease [Abstract]. American Thoracic Society 99th International Conference; 2003 May 16-21; Seattle. 2003:A035;Poster D92.
  • Reisner C, Morris A, Zhu J, Fischer T, Knobil K. Cilomilast is efficacious in chronic obstructive pulmonary disease [Abstract]. European Respiratory Journal 2003;22(Suppl 45):Abstract No:P530.
Lim 2004 {published data only}
  • Lim S, Zhu J, Lake P. Cilomilast decreases exacerbations and maintains lung function in patients with poorly reversible COPD. European Respiratory Journal 2004;24(Suppl 48):88s.
Nieman 1999 {unpublished data only}
  • Nieman RB, Taneja DT, Amit O, Benincosa LJ, Compton CH, Bethala VK, et al. The effects of low dose SB207499, a second generation, oral PDE4 inhibitor, in patients with COPD. European Respiratory Society Congress; 1999; Madrid. 1999:P2236.
Pascoe 2007 {unpublished data only}
  • Pascoe SJ, Bonner J, Hauffe S, Bohnemeier H. Gradual dose escalation of QAK423, a novel PDE4 inhibitor, significantly improves the tolerability [Abstract]. American Thoracic Society International Conference; 2007 May 18-23; San Francisco. 2007:Poster C31.
Reisner 2003 {published data only}
Rennard 2008 {published data only}
  • Rennard SI, Calverley PMA, Rempel A, Bredenbroker D, Martinez FJ. The effect of roflumilast treatment on exacerbations in patients with COPD results of a pooled analysis of two 1-year studies [Abstract]. American Thoracic Society International Conference; 2008 May 16-21; Toronto. 2008:A963.
Roflumilast JP708 {unpublished data only}
  • Ping J. Clinical pharmacology and biopharmaceutics review(s) [Application number 022522Orig1s000]. Centre for drug evaluation and research. (submitted 21 December 2010).
SB207499/040 {unpublished data only}
  • GSK CTR-040. A multicentre, open-label extension study to evaluate the safety, tolerability and efficacy of oral SB-207499 (15 mg twice daily) in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24044.pdf (accessed 25 May 2010).
SB207499/041 {unpublished data only}
  • GSK CTR-041. A multicenter open-label extension study to evaluate the safety, tolerability and efficacy of oral cilomilast (15 mg twice daily) in patients with chronic obstructive pulmonary disease. http://www.gsk-clinicalstudyregister.com/files/pdf/24045.pdf (accessed 25 May 2010).
Song 2005 {published data only}
  • Song Y, Wang C, Liao X, Wang Y, Li Q, Zhao Z, et al. Improvement in lung residual volume in patients with COPD roles of anti-inflammation activity of cilomilast. Respiratory 2005;10(Suppl 3):A135.
Spencer 2002 {published data only}
  • Spencer MD, Zhu J, Izard D. The direct costs of exacerbations in COPD and the effect of cilomilast treatment. European Respiratory Journal 2002;20(Suppl 38):245s.
Vestbo 2007 {published data only}
  • Vestbo J, Tan L, Atkinson G. A 6 week study of the efficacy and safety of UK 500,001 dry powder for inhalation (DPI) in adults with chronic obstructive pulmonary disease [Abstract]. European Respiratory Journal 2007;30(Suppl 51):612s [P3598].
Vestbo 2009 {published data only}
  • Vestbo J, Tan L, Atkinson G, Ward J. A controlled trial of 6-weeks' treatment with a novel inhaled phosphodiesterase type-4 inhibitor in COPD. European Respiratory Journal 2009;33(5):1039-44.
Wang 2005 {published data only}
  • Wang C, Song Y, Liao X. Efficacy and anti-inflammation activity of a selective phospodiesterase-4 inhibitor cilomilast in treatment of COPD. Chest 2005;128(4):262S-a.

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Calverley 2012 {published data only}
  • Effect of Roflumilast on Exacerbation Rate in Patients With COPD Treated With Fixed Combinations of LABA and ICS. A 52-week, Randomised Double-blind Trial With Roflumilast 500 µg Versus Placebo. The REACT Trial. http://clinicaltrials.gov/show/NCT01329029 (accessed 6 June 2013).
  • Calverley PM, Rabe KF, Goehring U, Kristiansen S, Kristiansen S, Martinez FJ. Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? the REACT study protocol. International Journal of COPD 2012;7(1):375-82.
Ferguson 2012 {published data only}
  • Ferguson GT, Rennard SI, Hanania NA, Zhu H, Siddiqui S, Sacks H. Roflumilast treatment in COPD patients taking a fixed-dose combination of long-acting β2 agonist (LABA) and inhaled corticosteroid (ICS): rationale and design of a prospective randomized controlled trial [Abstract]. American Journal of Respiratory and Critical Care Medicine 2012;185(Meeting Abstracts):A2946.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Agusti 2005
Barnes 2000
Barnes 2003
Barnes 2005
  • Barnes P. Theophylline in chronic obstructive pulmonary disease: new horizons. Proceedings of the American Thoracic Society Congress; 2005 May 20-25; San Diego 2005;2(4):334-9.
Boswell-Smith 2006
Calverley 2007
  • Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. New England Journal of Medicine 2007;356(8):775-89.
Celli 2004
Donohue 2005
  • Donohue J. Minimal clinically important differences in COPD lung function. COPD 2005;2:111-24.
Essayan 2001
Fabbri 2009
  • Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with long acting bronchodilators: two randomised clinical trials. Lancet 2009;374(9691):695-703.
Gamble 2003
  • Gamble E, Grootendorst DC, Brightling CE, Troy S, Qiu Y, Zhu J, et al. Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 2003;168:976-82.
GOLD 2013
  • Global Strategy for the Diagnosis, Management, Prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. Available from: http://www.goldcopd.org/ (accessed 6 June 2013).
Higgins 2008
  • Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated September 2008]. The Cochrane Collaboration, 2008. Available from www.cochrane-handbook.org.
Jones 2005
  • Jones P. St. George's Respiratory Questionnaire: MCID. COPD 2005;2:75-9.
Mathers 2005
  • Mathers C, Loncar D. Updated projections of global mortality and burden of disease, 2002-2030: data sources, methods and results. Evidence and Information for Policy Working Paper. World Health Organization, 2005.
RevMan 5.2
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
TORCH 2007
  • Calverley P, Anderson J, Celli B, Ferguson GT, Jenkins C, Jones P, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. New England Journal of Medicine 2007;356(8):775-89.
Torphy 1998
Torphy 1999
  • Torphy T, Barnette M, Underwood D, Griswold DE, Christensen SB, Murdoch RD, et al. Ariflo (SB 207499), a second generation phosphodiesterase 4 inhibitor for the treatment of asthma and COPD: from concept to clinic. Pulmonary Pharmacology and Therapeutics 1999;12(2):131-5.
Vignola 2004
White 2013
  • White W, Cooke G, Kowey P, Calverley P, Bredenbröker D, Goehring U, et al. Cardiovascular safety in patients receiving roflumilast for the treatment of chronic obstructive pulmonary disease. Chest 2013;144(3):758-65.