Article Text

PDF
OP0267 Initial Combination Therapy of Ambrisentan and Tadalafil in Connective Tissue Disease Associated Pulmonary Arterial Hypertension (CTD-PAH): Subgroup Analysis from the Ambition Trial
  1. J.G. Coghlan1,
  2. N. Galiè2,
  3. J.A. Barbera3,
  4. A.E. Frost4,
  5. H.A. Ghofrani5,
  6. M.M. Hoeper6,
  7. V.V. Mclaughlin7,
  8. A.J. Peacock8,
  9. G. Simonneau9,
  10. J.L. Vachiery10,
  11. C. Blair11,
  12. H. Gillies11,
  13. J.H. Harris12,
  14. J. Langley13,
  15. L.J. Rubin14
  16. on behalf of the AMBITION Study Group
  1. 1Royal Free Hospital, London, United Kingdom
  2. 2Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
  3. 3Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
  4. 4Department of Medicine, Section of Pulmonary and Critical Care, Baylor College of Medicine, Houston, United States
  5. 5Universities of Giessen and Marburg Lung Center (UGMLC), Iniversity of Giessen, Giessen
  6. 6Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
  7. 7Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, United States
  8. 8Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom
  9. 9National Reference Center for Severe Pulmonary Hypertension, Hôpital de Bicêtre, University Paris-Sud, Le Kremlin Bicêtre, France
  10. 10Département de Cardiologie, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium
  11. 11Research & Development, Gilead Sciences, Foster City, United States
  12. 12Research & Development
  13. 13GlaxoSmithKline, Brentford, United Kingdom
  14. 14Division of Medicine, University of California at San Diego, La Jolla, United States

Abstract

Background The AMBITION study, a randomized, double blind, event driven trial, previously reported that initial combination of ambrisentan and tadalafil significantly delayed time to clinical failure (TTCF) with a 50% reduction in risk compared with monotherapy of either drug.1,2

Objectives As CTD-PAH is a common form of PAH, and may respond differently to treatment, we explore the effect of initial combination therapy of ambrisentan (AMB) and tadalafil (TAD) in this subset of patients, in a post-hoc analysis.

Methods Treatment-naive PAH patients were randomised 2:1:1 to combination therapy of AMB 10mg and TAD 40mg (COMB), or monotherapy of AMB 10mg or TAD 40mg (MONO). The primary endpoint (EP) was TTCF (a composite of death, hospitalisation for worsening PAH, disease progression, or unsatisfactory long-term clinical response). Secondary EPs and safety was also assessed.

Results Of 500 patients recruited into the primary population, 187 (37%) had a diagnosis of CTD (COMB; n=103: MONO n=84), with the most common CTD being scleroderma (n=118). In CTD-PAH COMB reduced the risk of TTCF by 57% compared to MONO (HR 0.432; 95% CI: 0.242, 0.771), with a reduction in hospitalisations primarily driving the treatment effect. Secondary EPs are presented in table 1. Almost all patients experienced at least one Adverse Event (AE), and Serious AEs were experienced by 44% of COMB, 34% of AMB MONO and 50% of TAD MONO patients. AEs experienced in ≥10% COMB with a ≥2% difference versus both MONO were peripheral oedema, non-cardiac chest pain, anaemia, bronchitis, nasal congestion and back pain.

Conclusions In this post-hoc analysis, initial combination therapy of ambrisentan and tadalafil compared to monotherapy in CTD-PAH patients reduced the risk of clinical failure by 57%, and resulted in greater improvements in NTproBNP and exercise capacity. AEs were those typically associated with AMB and TAD, sometimes more frequent on combination therapy than monotherapy.

References

  1. Galie N, et al. ERS Annual Meeting 2014 (abstract)

  2. Rubin LJ, et al. CHEST Annual Meeting 2014 (abstract)

Acknowledgements This Study was Sponsored by Gilead Sciences and GlaxoSmithKline. Eli Lilly provided funding and study medication.

Disclosure of Interest J. G. Coghlan Grant/research support from: Actelion, Consultant for: Actelion, GlaxoSmithKline, Bayer, United Therapeutics, Pfizer, N. Galiè Grant/research support from: Actelion, Bayer, Eli Lilly, GlaxoSmithKline, Pfizer, Consultant for: Actelion, Bayer, Eli Lilly, GlaxoSmithKline, Pfizer, J. A. Barbera Grant/research support from: Actelion, Bayer, GlaxoSmithKline, Pfizer, Consultant for: Actelion, Bayer, GlaxoSmithKline, A. Frost Grant/research support from: Gilead, Actelion, Novartis, Bayer, United Therapeutics, Consultant for: Bayer, Actelion, Gilead, H. A. Ghofrani Grant/research support from: Actelion, Bayer, Ergonex, Pfizer, Consultant for: Actelion, Bayer, Ergonex, GlaxoSmithKline, Merck, Novartis, Pfizer, M. Hoeper Consultant for: Actelion, Bayer, GSK, Pfizer, Speakers bureau: Actelion, Bayer, GSK, Pfizer, V. Mclaughlin Grant/research support from: Actelion, Bayer, Consultant for: Actelion, Bayer, Gilead, United Therapeutics, A. Peacock Consultant for: GlaxoSmithKline, G. Simonneau Grant/research support from: Actelion, Bayer, GlaxoSmithKline, Consultant for: Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Actelion, Bayer, GlaxoSmithKline, J. L. Vachiery Grant/research support from: Actelion, Consultant for: Actelion, Bayer Schering, GlaxoSmithKline, C. Blair Shareholder of: Gilead, Employee of: Gilead, H. Gillies Employee of: Gilead, J. Harris Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, J. Langley Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, L. Rubin Consultant for: Gilead, Actelion, United Therapeutics, GeNO, Arena

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.