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Expert Review of Respiratory Medicine Volume 6, 2012 - Issue 3
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Inhaled treprostinil for the treatment of pulmonary arterial hypertension

Barbara L LeVarge Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. [email protected]
&
Richard N Channick Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
Pages 255-265 | Published online: 09 Jan 2014

References

  • Badesch DB, Champion HC, Sanchez MA et al. Diagnosis and assessment of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 54(Suppl. 1), S55–S66 (2009).
  • Simonneau G, Robbins IM, Beghetti M et al. Updated clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 54(Suppl. 1), S43–S54 (2009).
  • Humbert M, Sitbon O, Chaouat A et al. Pulmonary arterial hypertension in France: results from a national registry. Am. J. Respir. Crit. Care Med. 173(9), 1023–1030 (2006).
  • D’Alonzo GE, Barst RJ, Ayres SM et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann. Intern. Med. 115(5), 343–349 (1991).
  • Barst RJ, Rubin LJ, Long WA et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N. Engl. J. Med. 334(5), 296–302 (1996).
  • Galiè N, Manes A, Negro L, Palazzini M, Bacchi-Reggiani ML, Branzi A. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur. Heart J. 30(4), 394–403 (2009).
  • Humbert M, Sitbon O, Yaïci A et al.; French Pulmonary Arterial Hypertension Network. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur. Respir. J. 36(3), 549–555 (2010).
  • Barst RJ, Gibbs JS, Ghofrani HA et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J. Am. Coll. Cardiol. 54(Suppl. 1), S78–S84 (2009).
  • Channick RN, Simonneau G, Sitbon O et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 358(9288), 1119–1123 (2001).
  • Galiè N, Ghofrani HA, Torbicki A et al.; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N. Engl. J. Med. 353(20), 2148–2157 (2005).
  • Galiè N, Olschewski H, Oudiz RJ et al.; Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies (ARIES) Group. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation 117(23), 3010–3019 (2008).
  • Galiè N, Brundage BH, Ghofrani HA et al.; Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group. Tadalafil therapy for pulmonary arterial hypertension. Circulation 119(22), 2894–2903 (2009).
  • Gomberg-Maitland M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur. Respir. J. 31(4), 891–901 (2008).
  • Olschewski H, Rose F, Schermuly R et al. Prostacyclin and its analogues in the treatment of pulmonary hypertension. Pharmacol. Ther. 102(2), 139–153 (2004).
  • Barst RJ, Rubin LJ, McGoon MD, Caldwell EJ, Long WA, Levy PS. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann. Intern. Med. 121(6), 409–415 (1994).
  • Higenbottam TW, Spiegelhalter D, Scott JP et al. Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension. Br. Heart J. 70(4), 366–370 (1993).
  • Rubin LJ, Mendoza J, Hood M et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann. Intern. Med. 112(7), 485–491 (1990).
  • Patterson JH, Adams KF Jr, Gheorghiade M et al. Acute hemodynamic effects of the prostacyclin analog 15AU81 in severe congestive heart failure. Am. J. Cardiol. 75(3), 26A–33A (1995).
  • Mohler ER 3rd, Klugherz B, Goldman R, Kimmel SE, Wade M, Sehgal CM. Trial of a novel prostacyclin analog, UT-15, in patients with severe intermittent claudication. Vasc. Med. 5(4), 231–237 (2000).
  • Simonneau G, Barst RJ, Galie N et al.; Treprostinil Study Group. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am. J. Respir. Crit. Care Med. 165(6), 800–804 (2002).
  • Laliberte K, Arneson C, Jeffs R, Hunt T, Wade M. Pharmacokinetics and steady-state bioequivalence of treprostinil sodium (Remodulin) administered by the intravenous and subcutaneous route to normal volunteers. J. Cardiovasc. Pharmacol. 44(2), 209–214 (2004).
  • Gomberg-Maitland M, Tapson VF, Benza RL et al. Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am. J. Respir. Crit. Care Med. 172(12), 1586–1589 (2005).
  • Hiremath J, Thanikachalam S, Parikh K et al.; TRUST Study Group. Exercise improvement and plasma biomarker changes with intravenous treprostinil therapy for pulmonary arterial hypertension: a placebo-controlled trial. J. Heart Lung Transplant. 29(2), 137–149 (2010).
  • Tapson VF, Gomberg-Maitland M, McLaughlin VV et al. Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest 129(3), 683–688 (2006).
  • Olschewski H, Simonneau G, Galiè N et al.; Aerosolized Iloprost Randomized Study Group. Inhaled iloprost for severe pulmonary hypertension. N. Engl. J. Med. 347(5), 322–329 (2002).
  • Sandifer BL, Brigham KL, Lawrence EC, Mottola D, Cuppels C, Parker RE. Potent effects of aerosol compared with intravenous treprostinil on the pulmonary circulation. J. Appl. Physiol. 99(6), 2363–2368 (2005).
  • Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir. Med. 104(1), 9–21 (2010).
  • Aronoff DM, Peres CM, Serezani CH et al. Synthetic prostacyclin analogs differentially regulate macrophage function via distinct analog-receptor binding specificities. J. Immunol. 178(3), 1628–1634 (2007).
  • Lai YJ, Pullamsetti SS, Dony E et al. Role of the prostanoid EP4 receptor in iloprost-mediated vasodilatation in pulmonary hypertension. Am. J. Respir. Crit. Care Med. 178(2), 188–196 (2008).
  • Orie NN, Clapp LH. Role of prostanoid IP and EP receptors in mediating vasorelaxant responses to PGI2 analogues in rat tail artery: Evidence for Gi/o modulation via EP3 receptors. Eur. J. Pharmacol. 654(3), 258–265 (2011).
  • Falcetti E, Hall SM, Phillips PG et al. Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 182(9), 1161–1170 (2010).
  • Falcetti E, Flavell DM, Staels B, Tinker A, Haworth SG, Clapp LH. IP receptor-dependent activation of PPARgamma by stable prostacyclin analogues. Biochem. Biophys. Res. Commun. 360(4), 821–827 (2007).
  • Morrell NW, Adnot S, Archer SL et al. Cellular and molecular basis of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 54(Suppl. 1), S20–S31 (2009).
  • Yang J, Li X, Al-Lamki RS et al. Smad-dependent and smad-independent induction of id1 by prostacyclin analogues inhibits proliferation of pulmonary artery smooth muscle cells in vitro and in vivo. Circ. Res. 107(2), 252–262 (2010).
  • Cheng Y, Austin SC, Rocca B et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 296(5567), 539–541 (2002).
  • Junhui Z, Xingxiang W, Guosheng F, Yunpeng S, Furong Z, Junzhu C. Reduced number and activity of circulating endothelial progenitor cells in patients with idiopathic pulmonary arterial hypertension. Respir. Med. 102(7), 1073–1079 (2008).
  • Pendergrass SA, Hayes E, Farina G et al. Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury. PLoS One 5(8), e12106 (2010).
  • Atsuta H, Uchiyama T, Kanai H et al. Effects of a stable prostacyclin analogue beraprost sodium on VEGF and PAI-1 gene expression in vascular smooth muscle cells. Int. J. Cardiol. 132(3), 411–418 (2009).
  • Biscetti F, Gaetani E, Flex A et al. Peroxisome proliferator-activated receptor alpha is crucial for iloprost-induced in vivo angiogenesis and vascular endothelial growth factor upregulation. J. Vasc. Res. 46(2), 103–108 (2009).
  • Fontana M, Olschewski H, Olschewski A, Schlüter KD. Treprostinil potentiates the positive inotropic effect of catecholamines in adult rat ventricular cardiomyocytes. Br. J. Pharmacol. 151(6), 779–786 (2007).
  • Humbert M, Monti G, Brenot F et al. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am. J. Respir. Crit. Care Med. 151(5), 1628–1631 (1995).
  • Katsushi H, Kazufumi N, Hideki F et al. Epoprostenol therapy decreases elevated circulating levels of monocyte chemoattractant protein-1 in patients with primary pulmonary hypertension. Circ. J. 68(3), 227–231 (2004).
  • Pullamsetti SS, Savai R, Janssen W et al. Inflammation, immunological reaction and role of infection in pulmonary hypertension. Clin. Microbiol. Infect. 17(1), 7–14 (2011).
  • Raychaudhuri B, Malur A, Bonfield TL et al. The prostacyclin analogue treprostinil blocks NFkappaB nuclear translocation in human alveolar macrophages. J. Biol. Chem. 277(36), 33344–33348 (2002).
  • Zhou W, Hashimoto K, Goleniewska K et al. Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells. J. Immunol. 178(2), 702–710 (2007).
  • Ikeda Y, Yonemitsu Y, Kataoka C et al. Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary hypertension in rats. Am. J. Physiol. Heart Circ. Physiol. 283(5), H2021–H2028 (2002).
  • Strassheim D, Riddle SR, Burke DL, Geraci MW, Stenmark KR. Prostacyclin inhibits IFN-gamma-stimulated cytokine expression by reduced recruitment of CBP/p300 to STAT1 in a SOCS-1-independent manner. J. Immunol. 183(11), 6981–6988 (2009).
  • Centers for Disease Control and Prevention (CDC). Bloodstream infections among patients treated with intravenous epoprostenol or intravenous treprostinil for pulmonary arterial hypertension – seven sites, United States, 2003–2006. MMWR Morb. Mortal. Wkly Rep. 56(8), 170–172 (2007).
  • Kallen AJ, Lederman E, Balaji A et al. Bloodstream infections in patients given treatment with intravenous prostanoids. Infect. Control Hosp. Epidemiol. 29(4), 342–349 (2008).
  • Rich JD, Glassner C, Wade M et al. The effect of diluent pH on bloodstream infection rates in patients receiving IV treprostinil for pulmonary arterial hypertension. Chest 141(1), 36–42 (2012).
  • Voswinckel R, Enke B, Reichenberger F et al. Favorable effects of inhaled treprostinil in severe pulmonary hypertension: results from randomized controlled pilot studies. J. Am. Coll. Cardiol. 48(8), 1672–1681 (2006).
  • Wade M, Baker FJ, Roscigno R, DellaMaestra W, Hunt TL, Lai AA. Absolute bioavailability and pharmacokinetics of treprostinil sodium administered by acute subcutaneous infusion. J. Clin. Pharmacol. 44(1), 83–88 (2004).
  • Channick RN, Olschewski H, Seeger W, Staub T, Voswinckel R, Rubin LJ. Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in pulmonary arterial hypertension. J. Am. Coll. Cardiol. 48(7), 1433–1437 (2006).
  • McLaughlin VV, Gaine SP, Barst RJ et al.; Treprostinil Study Group. Efficacy and safety of treprostinil: an epoprostenol analog for primary pulmonary hypertension. J. Cardiovasc. Pharmacol. 41(2), 293–299 (2003).
  • Wade M, Baker FJ, Roscigno R et al. Pharmacokinetics of treprostinil sodium administered by 28-day chronic continuous subcutaneous infusion. J. Clin. Pharmacol. 44(5), 503–509 (2004).
  • McSwain CS, Benza R, Shapiro S et al. Dose proportionality of treprostinil sodium administered by continuous subcutaneous and intravenous infusion. J. Clin. Pharmacol. 48(1), 19–25 (2008).
  • Olschewski H, Rohde B, Behr J et al. Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension. Chest 124(4), 1294–1304 (2003).
  • Voswinckel R, Ghofrani HA, Grimminger F, Seeger W, Olschewski H. Inhaled treprostinil [corrected] for treatment of chronic pulmonary arterial hypertension. Ann. Intern. Med. 144(2), 149–150 (2006).
  • Walkey AJ, Fein D, Horbowicz KJ, Farber HW. Differential response to intravenous prostacyclin analog therapy in patients with pulmonary arterial hypertension. Pulm. Pharmacol. Ther. 24(4), 421–425 (2011).
  • Tyvaso® (treprostinil) inhalation solution, full prescribing information – Revised 2/2011. United Therapeutics, Silver Spring, MD, USA (2011).
  • Gotzkowsky SK, Dingemanse J, Lai A, Mottola D, Laliberte K. Lack of a pharmacokinetic interaction between oral treprostinil and bosentan in healthy adult volunteers. J. Clin. Pharmacol. 50(7), 829–834 (2010).
  • Wade M, Hunt TL, Lai AA. Effect of continuous subcutaneous treprostinil therapy on the pharmacodynamics and pharmacokinetics of warfarin. J. Cardiovasc. Pharmacol. 41(6), 908–915 (2003).
  • Voswinckel R, Reichenberger F, Enke B et al. Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension. Pulm. Pharmacol. Ther. 21(5), 824–832 (2008).
  • McLaughlin VV, Benza RL, Rubin LJ et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J. Am. Coll. Cardiol. 55(18), 1915–1922 (2010).
  • Benza RL, Seeger W, McLaughlin VV et al. Long-term effects of inhaled treprostinil in patients with pulmonary arterial hypertension: the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study open-label extension. J. Heart Lung Transplant. 30(12), 1327–1333 (2011).
  • Food and Drug Administration. Center for Drug Evaluation and Research. Medical Review – New Drug Application, NDA 22–387. US FDA, USA (2009).
  • Simonneau G, Rubin LJ, Galiè N et al.; PACES Study Group. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann. Intern. Med. 149(8), 521–530 (2008).
  • O’Callaghan DS, Savale L, Jaïs X et al. Evidence for the use of combination targeted therapeutic approaches for the management of pulmonary arterial hypertension. Respir. Med. 104 (Suppl. 1), S74–S80 (2010).
  • Hoeper MM, Leuchte H, Halank M et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur. Respir. J. 28(4), 691–694 (2006).
  • Galiè N, Hoeper MM, Humbert M et al.; ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur. Heart J. 30(20), 2493–2537 (2009).
  • Galiè N, Humbert M, Vachiéry JL et al.; Arterial Pulmonary Hypertension and Beraprost European (ALPHABET) Study Group. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. J. Am. Coll. Cardiol. 39(9), 1496–1502 (2002).
  • Barst RJ, McGoon M, McLaughlin V et al.; Beraprost Study Group. Beraprost therapy for pulmonary arterial hypertension. J. Am. Coll. Cardiol. 41(12), 2119–2125 (2003).
  • Rubin L, Parikh K, Pulido T et al. FREEDOM-M: efficacy and safety of oral treprostinil diethanolamine as monotherapy in patients with pulmonary arterial hypertension. Chest 140(4), abstract 1044 (2011).
  • Voswinckel R, Reichenberger F, Gall H et al. Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension. Pulm. Pharmacol. Ther. 22(1), 50–56 (2009).
  • Olschewski H, Ghofrani A, Walmrath D et al. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am. J. Respir. Crit. Care Med. 160(2), 600–607 (1999).
  • Dernaika TA, Beavin M, Kinasewitz GT. Iloprost improves gas exchange and exercise tolerance in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Respiration 79(5), 377–382 (2010).
  • Hegewald MJ, Elliott CG. Sustained improvement with iloprost in a COPD patient with severe pulmonary hypertension. Chest 135(2), 536–537 (2009).
  • Tissières P, Nicod L, Barazzone-Argiroffo C, Rimensberger PC, Beghetti M. Aerosolized iloprost as a bridge to lung transplantation in a patient with cystic fibrosis and pulmonary hypertension. Ann. Thorac. Surg. 78(3), e48–e50 (2004).

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