OP0267 Initial Combination Therapy of Ambrisentan and Tadalafil in Connective Tissue Disease Associated Pulmonary Arterial Hypertension (CTD-PAH): Subgroup Analysis from the Ambition Trial
Authors: J.G. Coghlan, N. Galiè, J.A. Barbera, A.E. Frost, H.A. Ghofrani, M.M. Hoeper, V.V. Mclaughlin, A.J. Peacock, G. Simonneau, J.L. Vachiery, C. Blair, H. Gillies, J.H. Harris, J. Langley, L.J. Rubin
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> 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.<sup>1,2</sup> <h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusions</h3> 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. <h3>References</h3> Galie N, et al. ERS Annual Meeting 2014 (abstract) Rubin LJ, et al. CHEST Annual Meeting 2014 (abstract) <h3>Acknowledgements</h3> This Study was Sponsored by Gilead Sciences and GlaxoSmithKline. Eli Lilly provided funding and study medication. <h3>Disclosure of Interest</h3> 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