National Horizon Scanning Centre. Tadalafil for pulmonary arterial hypertension. October 2007

Transcription

1 Tadalafil for pulmonary arterial hypertension October 2007 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The Research Programme is part of the National Institute for Health Research Technology for patient group

2 Tadalafil for pulmonary arterial hypertension Target group Pulmonary arterial hypertension (PAH): WHO functional class I, II, and IV. Background PAH is a diverse group of diseases characterised by a progressive increase of pulmonary vascular resistance, which leads to right ventricular failure and premature death if untreated 1. PAH includes idiopathic PAH (IPAH), formerly known as primary pulmonary hypertension, and pulmonary hypertension associated with various conditions such as connective tissue diseases, congenital systemic-to-pulmonary shunts, portal hypertension, and HIV infection 1. Pulmonary hypertension (of which PAH is a sub-category) is defined by a mean pulmonary artery pressure greater than 25 mmhg at rest or greater than 30 mmhg with exercise. Symptoms of PAH include dyspnoea, fatigue, chest pain, syncope, and oedema. PAH is classified according to clinical features and by functional capacity as classified by the New York Heart Association (NYHA) and the World Health Organisation (WHO). NYHA/WHO Classification of functional status of patients with pulmonary hypertension (PH) 2 Class Description I No limitation of usual physical activity; ordinary physical activity does not cause increased dyspnoea, fatigue, chest pain or pre-syncope. II Mild limitation of physical activity. There is no discomfort at rest, but normal physical activity causes increased dyspnoea, fatigue, chest pain or pre-syncope. Marked limitation of physical activity. There is no discomfort at rest, but less than ordinary activity causes increased dyspnoea, fatigue, chest pain or pre-syncope. IV Unable to perform any physical activity and who may have signs of right ventricular failure at rest. Dyspnoea and/or fatigue may be present at rest and symptoms are increased by almost any physical activity. Services for PAH were designated by the National Specialist Commissioning Advisory Group (NSCAG) from September There are currently seven designated centres (six adult and one paediatric) in England. Technology description Tadalafil is an orally active, selective, small-molecule phosphodiesterase (PDE) V inhibitor. PDE V is a significant PDE in the pulmonary vasculature and inhibition may potentiate nitric oxide-mediated pulmonary vasodilation and antiproliferative effects in patients with PAH. Tadalafil is already licensed for erectile dysfunction (as Cialis). Innovation and/or advantages Tadalafil is a PDE-V inhibitor that is taken once a day compared to three times a day for the other licensed PDE-V inhibitor, sildenafil. Developer Eli Lilly and company 2

3 Place of use Home care e.g. home dialysis Secondary care e.g. general, nonspecialist hospital General public e.g. over the counter Community or residential care e.g. district nurses, physio Tertiary care e.g. highly specialist services or hospital Other: Primary care e.g. used by GPs or practice nurses Emergency care e.g. paramedic services, trauma care NHS or Government priority area: Cancer Cardiovascular disease Children Diabetes Long term neurological conditions Mental health Older people Public health Renal disease Women s health None identified Other: Relevant guidance NICE are currently producing a multiple technology appraisal on drugs for PAH in adults. This is expected to be issued in April 2008 and will include assessment of: epoprostenol, iloprost (inhaled), bosentan, sitaxsentan and sildenafil. European Society of Cardiology guidelines on diagnosis and treatment of pulmonary arterial hypertension (2004) 2. British Cardiac Society guidelines: recommendations on the management of pulmonary hypertension in clinical practice (2001) 3. Clinical need and burden of disease The prevalence of PAH is estimated to be between 15 and 26 per million based on numbers recorded by the French and Scottish registries 4,5. This approximates to between 825 and 1,430 people in the UK. In England, in , IPAH was responsible for 3,889 hospital admissions and 4,386 finished consultant episodes, accounting for 17,096 bed days 6. In England and Wales, in 2005, there were 197 deaths registered due to IPAH 7. Existing comparators and treatments Drugs that target different mechanisms. Drug Trade name Company Mechanism of Action Route of administration Epoprostenol Flolan GlaxoSmithKline Prostanoid Continuous intravenous infusion Iloprost Ventavis Schering Health Prostanoid Inhalation via Care nebuliser Bosentan Tracleer Actelion Endothelin Oral, twice per day Pharmaceuticals receptor agonist Sitaxsentan Thelin Encysive Endothelin Oral, once per day receptor agonist Sildenafil Revatio Pfizer PDE-V Oral, three times inhibitor per day Functional class: & IV Other prostanoids used off-licence: iloprost (intravenous) and treprostinil (intravenous or subcutaneous continuous infusions). Calcium channel blockers - work in a minority of patients with PAH. Management of symptoms: diuretics for oedema anticoagulants for preventing clots in the blood vessels inhaled oxygen 3

4 digoxin Efficacy and safety Trial name or code PHIRST-1 / H6D-MC-LVGY Sponsor Eli Lilly; ICOS Corporation. Status Ongoing Location US; Canada; Europe (inc. UK); Japan. Design Randomised, double blind, placebo control Participants in trial n=400; age 12 years; PAH that is either idiopathic, related to collagen vascular disease, anoerexigen use, atrial septal defect, or repaired congenital systemic to pulmonary shunt. WHO functional class I-IV. Follow-up 16 weeks Primary outcome 6 minute walk distance change from baseline to week 16. Secondary outcomes WHO functional class; Borg dyspnoea; cardiopulmonary haemodynamics; quality of life. Estimated cost and cost impact The cost of tadalafil for PAH has not been determined. Tadalafil as Cialis would cost around 50 for 40 mg a day for 4 days ( 350 for 28 days) a. The cost of other drugs licensed for PAH are: Drug Cost a Dose Approx. cost per annum Epoprostenol per 500 µg vial 9.2 ng/kg/min 40 ng/kg/min 25,158 94,951 Iloprost per 2ml (20 µg) vial µg, 6-9 times daily 11,600-29,600 Bosentan per 62.5 mg or mg twice daily, 20,075 mg tablet max 250 mg twice daily b Sitaxsentan per 100 mg tablet 100 mg once daily 20,075 Sildenafil 4.15 per 20 mg tablet 20 mg three times daily 4,545 Potential or intended impact speculative Patients Reduced morbidity Quicker, earlier or more accurate diagnosis or identification of disease Reduced mortality or increased survival Other: Improved quality of life for patients and/or carers Non identified Services Increased use Service reorganisation required Staff or training required Decreased use Other: Non identified a Based on British National Formulary 53, March 2007 b Expert comment suggests that bosentan is rarely used at 250mg twice daily the cost calculations are therefore based on mg twice daily 4

5 References 1 Simonneau G, Galie N, Rubin LJ et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004;43 Suppl 1:S Galiè N, Torbicki A, Barst R et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension: The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 2004;25: British Cardiac Society Guidelines and Medical Practice Committee. Recommendations on the management of pulmonary hypertension in clinical practice. Heart (suppl I):i1-i13. 4 Humbert M, Sitbon O, Chaouat A. Pulmonary arterial hypertension in France. Results from a national registry AJRCCM 2006;173: Peacock AJ, Murphy NF McMurray JJV et al. An epidemiological study of pulmonary arterial hypertension in Scotland. Eur. Respir. J., published online before print 14/3/07 as doi:doi: / The Information Centre for health and social care, Primary Diagnosis HES , HES Online, Accessed 13/4/07. 7 Office for National Statistics. Mortality statistics: Disease of the nervous system: underlying cause, series DH2, no. 32, The National Institute for Health Research Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0)