After 3.5 year process, NICE recommends Revolade (eltrombopag) for treatment of chronic immune thrombocytopenic purpura (ITP), UK
Adult patients in England and Wales living with chronic immune (idiopathic) thrombocytopenic purpura (cITP), an immune disorder associated with low blood platelet counts, will now be able to access Revolade® (eltrombopag) on the National Health Service (NHS), following final guidance (known as Technology Appraisal Guidance – TAG) issued today by the National Institute for Health and Care Excellence (NICE).
Professor Adrian Newland, Clinical Director for Pathology, The Royal London Hospital commented: “I was very pleased to see that NICE has recognised the clinical value and cost-effectiveness of eltrombopag in their guidance. With their recommendation on the use of eltrombopag within its licensed indication, we now have an important addition to the treatment options for patients with severe or refractory disease. When added to conventional immunosuppressive therapy, eltrombopag, an oral thrombopoietin receptor agonist, increases response rates compared to placebo and in some patients allows reduction or discontinuation of concomitant treatments for chronic ITP. The option to prescribe this agent will be of benefit to patients with chronic ITP and access to an oral agent is welcome.”
The NICE TAG recommends eltrombopag within its licensed indication for the treatment of adults with cITP, if:
- their condition is refractory to standard active treatments and rescue therapies, or
- they have severe disease and a high risk of bleeding that needs frequent courses of rescue therapies and
- the manufacturer provides eltrombopag with the discount agreed in the patient access scheme.
Eltrombopag is an oral thrombopoietin receptor agonist (TPO-RA) taken at home as a once-daily tablet. Eltrombopag stimulates the growth and maturation of cells in the bone marrow (megakaryocytes) that produce platelets, thereby increasing platelet production. The only other licensed TPO-RA, which is also recommended by NICE, is N-plate (romiplostim); romiplostim is given in the form of a weekly injection.
Erik Van Snippenberg, General Manager, GlaxoSmithKline (GSK) UK commented: “This has been a lengthy three and a half year long appraisal process. We are pleased that NICE has recommended eltrombopag and that the small number of cITP patients in England and Wales are granted access to an alternative treatment option offering the benefit of oral convenience. With eltrombopag we hope to ultimately make a meaningful difference in the quality of life of cITP patients and contribute to potential savings for the NHS.”
Adverse effects associated with eltrombopag include headache, insomnia, paraesthesia, cataract, dry eye, nausea, diarrhoea, constipation, upper abdominal pain, hepatobiliary disorders, rash, pruritus, alopecia, arthralgia, myalgia, muscle spasm, bone pain, fatigue and oedema peripheral. Other serious side effects include bleeding after stopping treatment, high platelet counts and risk of blood clots, as well as liver and bone marrow problems.
In patients with cITP, the immune system prematurely destroys platelets or impairs platelet production so that platelets are lost from the circulation faster than they can be replaced from the bone marrow, where they are made. This results in a shortage of platelets (thrombocytopenia). While some patients are asymptomatic or develop only mild bruising, others may have serious bleeding, which affects their quality of life and in some instances may be fatal. It is estimated that ITP currently affects 50 in 100,000 people in the UK.
Eltrombopag is indicated for adult chronic immune (idiopathic) thrombocytopenic purpura (cITP) splenectomised (spleen has been removed) patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). Eltrombopag may be considered as second line treatment for adult non-splenectomised patients where surgery is contraindicated.
Eltrombopag treatment should remain under the supervision of a physician who is experienced in the treatment of haematological diseases.
Further information can be found in the Summary of Product Characteristics.
About cITP (per GSK’s submission to NICE)
Primary immune thrombocytopenia (ITP), formerly known as idiopathic thrombocytopenic purpura, is an orphan disease. The prevalence of ITP in the UK is estimated at 50 in 100,000 people.
It is uncertain what causes ITP, in which increased platelet destruction and impaired platelet production, lead to low platelet counts and impaired blood clotting. The resulting bleeding symptoms range from mild bruising to serious haemorrhage, which can be fatal.
Patients who have had ITP for more than 12 months are considered to have cITP. Quality of life is adversely affected in patients with cITP, with a fear of bleeding limiting patients’ daily activities.
The aims of treatment are to reduce the risk of bleeding by elevating platelet count, whilst minimising treatment related side effects. The management of ITP is complex; following first line treatment with corticosteroids or immunoglobulins there is no clearly defined treatment pathway and the clinical trial evidence is scarce. It is generally accepted that management of ITP is tailored to the individual patient depending on their symptoms, platelet count, lifestyle and the adverse events associated with the different therapies.[3,9] Splenectomy (removal of the spleen) is a potentially curative treatment option for cITP but is invasive, irreversible and not appropriate for all patients. Splenectomy provides an initial haemostatic response in 80 per cent of patients and around 66 per cent will have a sustained complete response. About 14 per cent of patients do not respond and approximately 20 per cent of responders relapse following splenectomy. Patients typically cycle through several therapy options, some of which have significant side effects and most of which are not licenced as treatments for ITP.
Eltrombopag is one of two thrombopoietin receptor agonists (TPO-RAs) licensed for the treatment of cITP. The use of eltrombopag in cITP is supported by robust evidence from randomised controlled trials.[11-16]
[1.] National Institute of Clinical Excellence (NICE): Eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura (rev TA205): Technology Appraisal Guidance. July 2013. http://guidance.nice.org.uk/TA293
[2.] Revolade Summary of Product Characteristics (SPC): June 2012.
[3.] Stasi R. Immune thrombocytopenic purpura: the treatment paradigm. Eur J Haem 2009; 82 (suppl. 71): 13-19.
[4.] National Institute for Health and Care Excellence. Final appraisal determination: Romiplostim for the treatment of chronic immune (idiopathic) thrombocytopenic purpura. Available at: http://www.nice.org.uk/nicemedia/live/12027/53541/53541.pdf (accessed 29 May 2013).
[5.] Provan D. Characteristics of immune thrombocytopenic purpura: a guide for clinical practice. Eur J Haem 2009; 82 (suppl.71): 8-12.
[6.] Bennett D et al, Prevalence of Diagnosed Adult Immune Thrombocytopenia in the United Kingdom. Adv Ther 2011; 28 (12): 1096-1104.
[7.] Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168-186.
[8.] Michel M. Immune thrombocytopenic purpura: epidemiology and implications for patients. Eur J Haem 2009; 82 (suppl.71): 3-7.
[9.] Cuker A and Cines D, Immune Thrombocytopenia, ASH Education Book 2010; 1: 377-384.
[10.] ITP Support Association. What is childhood ITP? Available at: http://www.itpsupport.org.uk/childhooditp.htm (accessed 29 May 2013).
[11.] Cheng G, Saleh MN, Bussell JB, et al. Oral eltrombopag for the long-term treatment of patients with chronic Idiopathic Thrombocytopenic Purpura: Results of a phase III, double-blind, placebo-controlled study (RAISE). Oral presentation at American Society of Hematology Annual Meeting 2008. Blood 2008; 112 (11): Abstract no. 400.
[12.] Bussel J, Provan A, Shamsi T, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopatic thrombocytopenic purpura : a randomised, double-blind, placebo-controlled trial. The Lancet 2009; 373: 641-48.
[13.] Bussel JB, Cheng G, Saleh M, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007; 357: 2237-47.
[14.] Bussell J, Cheng G, Saleh MN, et al. Safety and efficacy of long-term treatment with oral eltrombopag for chronic idiopathic thrombocytopenic purpura (ITP). Presented at American Society of Hematology Annual Meeting 2008. Blood 2008; 112 (11): Abstract no. 3432.
[15.] Bussel J, Psaila B, Saleh M, et al. Efficacy and safety of repeated intermittent treatment with eltrombopag in patients with chronic idiopathic thrombocytopenic purpura. Poster presentation at American Society of Hematology Annual Meeting 2008. Blood 2008; 112 (11): Abstract no. 3431.
[16.] Cheng G, Saleh M, Bussell J, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. The Lancet, Volume 377, Issue 9763, 29 January 2011-4 February 2011, Pages 393-402 INCLUDING DEPARTMENT OF ERROR.