Northern Treatment Advisory Group

Transcription

1 Northern Treatment Advisory Group Ferric Maltol (Feraccru ) for the treatment of iron deficiency Lead author: Daniel Hill Regional Drug & Therapeutics Centre (Newcastle) September

2 Summary Iron deficiency occurs when the body s iron demand is not met by iron absorption from the diet. Iron deficient anaemia develops as iron deficiency becomes more severe. Iron deficient anaemia occurs in 2-5% of adult men and postmenopausal women in the developed world. Ferric maltol (Feraccru ) is an oral iron preparation of ferric (Fe 3+ ) combined with the sugar derivate maltol. This stable complex remains intact before it is absorbed across the gastro-intestinal tract. A reduction in free iron in the gastro-intestinal tract increases bioavailability and decreases adverse effects. Ferric maltol had a license extension by the EMA in March The indication was widened from in adults with iron deficiency anaemia in patients with IBD to adults with iron deficiency. There is no new clinical evidence to support the license extension of ferric maltol. Two further clinical trials are still ongoing. Please refer to the London Medicines Evaluation Network Review from 2016 for a review of the available evidence and safety data for ferric maltol. Ferric maltol is not included in current British Society of Gastroenterology iron deficiency anaemia guidelines, but these shall be updated by the summer One month s treatment with ferric maltol costs There is potential cost savings from a reduction in use of intravenous iron. It is hypothesised that ferric maltol could be used as a second line treatment for mild-moderate iron deficient anaemia. In comparison to the current treatment pathway for iron deficient anaemia there is potential cost saving of 49,993 per 100,000 of the population if ferric maltol was initiated in primary care. However if initiated in secondary care there would be an additional cost of 38,394 in comparison to the current pathway. Intravenous iron is currently funded by secondary care. Primary care would absorb the responsibility and cost of prescribing ferric maltol. Northern Treatment Advisory Group, September

3 Introduction Iron deficiency is a condition in which there are insufficient iron stores with signs and / or symptoms of a compromised supply of iron stores to tissues. Anaemia develops as the iron deficiency becomes more severe. Iron deficiency anaemia (IDA) occurs when there is a reduction in iron stores and a subsequent drop in haemoglobin. Mildmoderate iron deficiency can occur without anaemia but tissues can still be functionally impaired. 1 IDA occurs in 2-5% of adult men and postmenopausal women in the developed world. Common causes of IDA include menstruation, gastric and colonic cancer, malabsorption, poor dietary intake and the use of NSAIDs. 2 The World Health Organisation (WHO) defines anaemia as haemoglobin less than 13 g/dl in men or less than 12g/dl in non-pregnant women. 1 A reduced mean cell volume is common in IDA but low serum ferritin is the most powerful test for iron deficiency. 2 The British Society of Gastroenterology (BSG) and NICE recommend that oral iron preparations such as ferrous sulphate are first line treatments for IDA. 2,3 Up to 10% of patients treated with oral iron will develop intolerance in the form of constipation, nausea or diarrhoea. Intolerance to oral iron supplements can be managed by: 3 Offering a laxative to people with constipation Offering reassurance to people who have black stools Recommending iron is taken with meals Reducing the frequency of the iron supplement Use alternative iron compounds such as ferrous fumarate or ferrous gluconate If patients are unable to tolerate oral iron or those who do not respond, traditionally the next line of treatment would have been parenteral iron via secondary care. 4 The BSG will publish a new management of IDA guideline by the summer of 2019 which will consider the place of ferric maltol in the treatment of IDA. 5 Anaemia is a known burden on health and reduces quality of life of those affected. 6 There were 19,921 emergency hospital admissions in England during 2014/15 with a primary diagnosis of IDA. It is estimated this was a potential avoidable cost of 54 million. 7 Ferric maltol (Feraccru, Shield Therapeutics) had a license extension by the EMA in March The indication was widened from in adults with iron deficiency anaemia in patients with IBD to adults with iron deficiency. 8 Ferric maltol is a stable ferric complex. The complex remains intact before it is absorbed across the gastro- Northern Treatment Advisory Group, September

4 intestinal tract. This increases bioavailability and reduces the amount of free iron in the gastro-intestinal tract, potentially reducing gastro-intestinal toxicity associated with free iron. 9,10 In September 2016 recommended the use of ferric maltol as an alternative option in patients with mild to moderate IDA with IBD who have tried at least two oral ferrous salts and have a reported intolerance to oral ferrous salts due to adverse effects after an adequate trial. Initiation and prescribing of ferric maltol should be carried out by an IBD specialist. 11 Table 1: Iron deficiency and iron deficiency anaemia in common conditions in adults 12 (Adapted from Feracrrcu - Formulary support pack) Conditions Prevalence IDA Prevalence ID Menorrhagia Inflammatory bowel disease Iron deficiency anaemia this occurs in about twothirds of women with heavy menstrual bleeding. Prevalence of anaemia on average ranges from 33-40% in adult patients with IBD. ID is estimated to affect 55 80% of adult patients. Chronic kidney disease UK population data shows the prevalence of haemoglobin levels below 11 g/dl is 2.7% in those with a glomerular filtration rate (GFR) above 60 ml/minute. This increases to 2.9% in those with a GFR between 45 and 59 ml/minute (CKD stage 3A), 4.1% in those with a GFR between 30 and 44 ml/minute (CKD stage 3B) and 10% in those with a GFR below 30 ml/minute (CKD stages 4 and 5). ID is estimated to affect 24 85% of patients. Chronic heart failure Anaemia in CHF is present in 25-40% of patients. ID is estimated to affect 37 61% of patients. Gastrectomy/achlorhydria Coeliac disease Vegan diet Cancer IDA is reported in up to 46% of cases of subclinical coeliac disease and may be the presenting feature. Approximately 60-70% of people with solid or haematological cancers, who have chemotherapy, develop anaemia. Long-term follow-up of patients after gastrectomy showed a high rate of iron deficiency (70-90%), which appears to correct with iron supplementation. Anaemia is found in 32 69% of adult patients with 80% being iron deficient. 40 percent of vegans 19 to 50 years of age were iron deficient. Iron deficiency is reported in 32% to 60% of patients with cancer, most of whom are also anaemic. Northern Treatment Advisory Group, September

5 Figure 1: Treatment pathway proposed by manufacturer of ferric maltol (Feraccru ) (Adapted from Feracrrcu - Formulary support pack) Clinical evidence There is no new clinical evidence to support the license extension of ferric maltol. The EMA granted the license extension on the base that patients with inflammatory bowel disease (IBD) are the worst case population who are commonly intolerant to oral ferrous products. 8 For information regarding the clinical evidence of ferric maltol in patients with IBD please refer to the London Medicines Evaluation Network Review from There are currently two ongoing clinical trials involving ferric maltol. These include ferric maltol vs parenteral iron in IBD and ferric maltol vs placebo in CKD. At the time of writing no data is published for either of these studies. 13,14 Safety In addition to clinical evidence there is also no further information regarding the safety of ferric maltol with this license extension. For information regarding the safety of ferric maltol in patients with IBD please refer to the London Medicines Evaluation Network Review from At the time of writing there have been no reports of adverse drug reactions via the Yellow Card scheme for ferric maltol. 15 Northern Treatment Advisory Group, September

6 Specialist opinion Specialists working within the iron deficiency anaemia services at The Newcastle upon Tyne Hospitals NHS Foundation Trust believe that ferric maltol will have benefit in the following patient groups: Hypersensitivity to IV iron Hypo-phosphataemia to IV iron Patients dependent on transfusions / IV iron Failed two oral iron preparations or iron resistant Patients who are house bound or have reduced mobility and unable to access secondary care facilities Patients post complex GI surgery with IDA in whom oral intolerance is likely to cause a deterioration in their bowel symptoms They believe that a ferric maltol would require a shared care protocol. At the time of writing they have two patients who have received ferric maltol since its license extension. One has responded and no longer requires IV iron, the other has not. 16 Northern Treatment Advisory Group, September

7 Cost analysis Cost of oral Iron Drug Pack size Pack cost Doses per day Cost per month Cost per 12 week course Ferrous sulphate 200mg Ferrous fumarate 210mg Ferrous gluconate 300mg Ferric Maltol 30mg (Costs taken from emims June 2018) Cost of IV iron Drug Drug cost per gram Fe (ex VAT) Cosmofer (Iron dextran) Venofer (Iron sucrose) Ferinject (Ferric carboxymaltose) Monofer (Iron isomaltoside) (Costs taken from emims June 2018) Drug cost per gram Fe (inc VAT) Infusion time hours mins 3 x week until course complete mins mins Northern Treatment Advisory Group, September

8 Cost of a course for 70kg patient with Hb 11 (g/dl) Drug Dose Cost (inc VAT) Cosmofer (Iron dextran) Venofer (Iron sucrose) Ferinject (Ferric carboxymaltose) Monofer (Iron isomaltoside) 1250mg (In 1 infusion) mg (In 6 infusions) mg (In 2 infusions) mg (In 2 infusions) Budget impact of each treatment option for 12 week treatment / course Ferrous Sulphate Ferrous Fumarate Ferric Maltol (Primary care initiation) Ferric Maltol (Secondary care initiation) Drug cost (inc VAT) Outpatient visit* Ferinject (2 x infusions) (inc VAT) GP visit Nurse time* x 2 Total Cost per patient Total cost per 100,000 population (Assuming 10% receive treatment) , , ,671 Total cost per 100,000 population based on drug costs alone (Assuming 10% receive treatment) (*Prices obtained from National tariff 18/19) ,686 84, ,421 Northern Treatment Advisory Group, September

9 Future potential pathway Primary care initiation (Assume ferrous sulphate given as first PO iron) Prevalence of IDA in men = 3% Prevalence of IDA in women = 8% Therefore 5.5% of general population will have IDA Per 100, will have IDA 10% will have severe anaemia and have treatment with IV iron ( 345,191) 4950 will receive oral iron ( 230,422) 10% will not tolerate oral iron 495 per 100,000 potentially suitable to receive ferric maltol according to figure 1 ( 89,496) 13% failure rate with ferric maltol will then receive IV iron 64 per 100,000 will receive IV iron ( 40,167) Mild to moderate IDA = Oral iron Ferric maltol IV Iron Severe IDA = IV iron Cost per 100,000 - ( 345,191) + ( 230,422) + ( 89,496) + ( 40,167) = 705,276 Future potential pathway Secondary care initiation (Assume ferrous sulphate given as first PO iron) Prevalence of IDA in men = 3% Prevalence of IDA in women = 8% Therefore 5.5% of general population will have IDA Per 100, will have IDA 10% will have severe anaemia and have treatment with IV iron ( 345,191) 4950 will receive oral iron ( 230,422) 10% will not tolerate oral iron 495 per 100,000 potentially suitable to receive ferric maltol according to figure 1 ( 177,883) 13% failure rate with ferric maltol will then receive IV iron 64 per 100,000 will receive IV iron ( 40,167) Mild to moderate IDA = Oral iron Ferric maltol IV Iron Severe IDA = IV iron Cost per 100,000 - ( 345,191) + ( 230,422) + ( 177,883) + ( 40,167) = 793,663 Northern Treatment Advisory Group, September

10 Current pathway (Assume ferrous sulphate given as first line PO iron and ferrous fumarate as second) Prevalence of IDA in men = 3% Prevalence of IDA in women = 8% Therefore 5.5% of general population will have IDA Per 100, will have IDA 10% will have severe anaemia and have treatment with IV iron ( 345,191) 4950 will receive oral iron ( 230,422) 10% will not tolerate oral iron 495 per 100,000 will receive a second PO iron ( 24,007) Assume 50% failure rate with second PO iron will then receive IV iron 248 per 100,000 will receive IV iron (155,649) Mild to moderate IDA = Oral iron Alternative oral iron IV Iron Severe IDA = IV iron Cost per 100,000 - ( 345,191) + ( 230,422) + ( 24,007) + (155,649) = 755,269 Cost saving for future pathway primary care initiation = - 49,993 Additional cost for future pathway secondary care initiation = 38,394 Points to consider There has been no new published data to support the license extension of ferric maltol. Ferric maltol is not included in current BSG iron deficiency anaemia guidelines but these shall be updated in The initial cost of prescribing ferric maltol is significant in comparison to other oral iron preparations. However there are potential cost savings by fewer referrals to secondary care, a reduction in IV iron and associated costs including nursing time. The majority of cost savings would come from a reduction in the use of IV iron. IV iron is currently funded by secondary care. Primary care would absorb the responsibility and cost of prescribing ferric maltol. The reduction in IV iron use would increase capacity of day units in secondary care. Northern Treatment Advisory Group, September

11 Author s declaration. The lead author has no relevant interests to declare. References 1. WHO. Iron Deficiency Anaemia; Goddard AF et al. Guidelines for the management of iron deficiency anaemia. Gut 2011;60: NICE. Clinical Knowledge Summary. Anaemia - Iron Deficiency BMJ. Best Practice Iron deficient anameia Personal Correspondence - British Society of Gastroenterology 6. Smith R. The Clinical and Economic Burden of Anemia. Am J Manag Care 2010;16: Goddard AF, Phillips,C. An economic report on the hidden cost of anaemia management European Assessment Report - Feraccru Procedure No. EMEA/H/C/002733/II/ Summary of product characteristics - Ferracru 10. London Medicines Evaluation Network Review - Ferric Maltol (oral Feraccru ) for the treatment of iron deficiency anaemia in adults with inflammatory bowel disease Treatment Appraisal: Decision Summary (Ferric Maltol) Shield. Feraccru (ferric maltol) - Formulary Support Pack Safety and Efficacy Study of Oral Ferric Maltol Compared to Intravenous Iron To Treat Iron Deficiency Anaemia in IBD - NCT Study With Oral Ferric Maltol for the Treatment of Iron Deficiency Anemia in Subjects With Chronic Kidney Disease (AEGIS-CKD) - NCT Personal Correspondence MHRA - Yellow Card Data (Ferric Maltol). 16. Personal Correspondence - Iron Deficiency Anaemia Services - NUTH. Northern Treatment Advisory Group, September