Once-daily oral treatment offers patients a clinically and cost-effective option
Patients in England and Wales living with an immune disorder causing low blood platelet count, known as ” cITP”, chronic immune (idiopathic) thrombocytopenic purpura, are one step closer to being able to access Revolade® (eltrombopag) on the National Health Service (NHS). Revolade is an oral thrombopoietin receptor agonist (TPO-RA) which stimulates platelet production in bone marrow, to reduce bruising and bleeding. The National Institute for Health and Clinical Excellence (NICE) has issued draft guidance recommending Revolade for the treatment of adults with cITP:
- who have had a splenectomy (spleen removed) and whose condition is refractory to other treatments (for example, corticosteroids or immunoglobulins),
- or as second-line treatment in adults who have not had a splenectomy because surgery is contraindicated,
- and, in both cases, provided that GSK complies with an agreed patient access scheme1. The access scheme provides a straight discount with no additional administrative burden for the NHS.
The draft guidance will now undergo consultation. Final guidance is expected in the second quarter of 2013.
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.2,3 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.4
Revolade offers a clinical benefit for patients with cITP by increasing platelet counts, reducing bleeding and the need for additional medicines to prevent or stop bleeding, as demonstrated in the largest randomised controlled trial in cITP to date.5 Revolade is a once-daily tablet which can be taken long-term, at home. The only other licensed TPO-RA is N-plate (romiplostim), which is approved by NICE and given in the form of a weekly injection. Adverse effects associated with Revolade 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 e! ffects include bleeding after stopping treatment, high platelet counts and risk of blood clots, as well as liver and bone marrow problems.6
cITP, while relatively rare, can nonetheless be a debilitating and worrying condition and may place restrictions on lifestyle, such as participation in sports or manual work.7 The Appraisal Committee recognised from the evidence presented by patient experts and clinicians that the nature of the condition impacts both the physical and emotional wellbeing of patients. Bleeding related anxiety may significantly affect both patients and families.
Erik Van Snippenberg, General Manager, GlaxoSmithKline (GSK) UK commented: “We are delighted that NICE has recognised the value of Revolade for this patient group – particularly as we acknowledge that assessing the cost effectiveness of medicines can be a challenge when numbers of eligible patients are small. GSK is committed to enabling patients to access the right treatments, ensuring that the NHS gets value for money and that we achieve a fair return for the medical innovations that we research and develop. We look forward to working with NICE to complete the appraisal process over the coming weeks.”
Revolade (eltrombopag) is indicated for adult chronic immune (idiopathic) thrombocytopenic purpura (ITP) splenectomised 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.
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 incidence of ITP is estimated to be between 1.6 and 3.9/100,000/year, with a UK prevalence estimated at 50/100,000.
ITP is a disorder of uncertain aetiology involving increased platelet destruction and impaired platelet production, leading to low platelet counts and impaired blood clotting. The resulting bleeding symptoms range from mild bruising to serious haemorrhage, which can be fatal.
Patients whose disease has lasted for more than 12 months are considered to have chronic ITP (cITP). They are often unresponsive to one or more agents and their disease is associated with significant morbidity, an impaired quality of life and increased mortality.
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 RCT 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.
Splenectomy is a potentially curative treatment option for cITP but is invasive, irreversible and not appropriate for all patients. Splenectomy provides an initial hemostatic response in 70-80% of patients. About 15-25 % of patients relapse following splenectomy and around 66% will have a sustained comp! lete response. Patients typically cycle through several therapy options, some of which have significant side effects and most of which are not licensed as treatments for ITP.
Eltrombopag is one of two thrombopoietin receptor agonists (TPO-RAs) licensed for the treatment of cITP. In contrast to other medicines used to treat this condition, the use of both these medicines in cITP is supported by robust evidence from randomised controlled trials.
Rescue treatments such as intravenous corticosteroids or immunoglobulin (IVIg) may be given when a patient bleeds or is considered at high risk of bleeding. These are used either as an adjunct to the patient’s primary therapy or once non-rescue treatment options have been exhausted.
1. National Institute for Health and Clinical Excellence Appraisal consultation document – Eltrombopag for treating chronic immune (idiopathic) thrombocytopenic purpura (review of technology appraisal 205). Issue date: December 2012. Accessed December 2012
2. Provan D. Characteristics of immune thrombocytopenic purpura: a gudie for clinical practice. Eur J Haem 2009; 82 (suppl.71): 8-12.
3. Thrombocytopenia. Available at www.netdoctor.co.uk (accessed Dec 2012).
4. Portielje JE, Westendorp RG, Kluin-Nelemans HC, Brand A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 2001; 97(9):2549-2554
5. Gregory Cheng 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.
6. Revolade SMPC
7. Michel M. Immune thrombocytopenic purpura: epidemiology and implications for patients. Eur J Haem 2009; 82 (suppl.71): 3-7.