Hambleton, Richmondshire and Whitby Clinical Commissioning Group Governing Body

Item 20 Hambleton, Richmondshire and Whitby Clinical Commissioning Group Governing Body Date of Meeting: 28 May 2015 Title: Report for: Treatment Advisory Group Recommendations to Clinical Commissioning Group Decision This Report includes /supports the following CCG aims: 1. Involve people in their care and as part of that we will encourage self-care Tick 2. Buy quality services 3. Change services for the better and in doing so we will provide care as close to home as possible that is easily accessible 4. Use the money we have in the best possible way The CCG values are: Integrity Transparency Collaborative Focus Action Energy Courage Page 1

Hambleton, Richmondshire and Whitby Clinical Commissioning Group Governing Body 28 May 2015 Treatment Advisory Group Recommendations to CCG 1. Introduction and Purpose The North Yorkshire and Humber Treatment Advisory Group (TAG) reviews the evidence for new treatments that have not to date been provided within our area. It also reviews existing treatments where evidence has recently emerged to merit reconsideration of its place in therapy. This paper assists the Governing Body to determine its own commissioning positions in response to the recommendations of the TAG. 2. Background Information TAG recommendations are made to the CCG following consultation with specialists from across North Yorkshire, Humber and associated providers. This assists the CCG Prescribing Lead and his team to make a more informed proposal for the CCG s commissioning position that is fitting with the needs of the broader local population and incorporates the opinion of local specialists and neighbouring commissioners of national health services. The TAG is hosted by the North Yorkshire and Humber Commissioning Support Unit (CSU), with their Service Delivery and Assurance Team and Medicines Management Team playing key roles in the delivery of this service. 3. Key Issues The purpose of the TAG process is to assist the CCG to make commissioning decisions on healthcare interventions, including drugs, based on clinical outcomes, value for money and affordability. It will also assist the CCG in the development of care pathways supported by general commissioning policies and established commissioning arrangements with providers for those treatments that are commissioned. The HRW CCG GP Prescribing Lead s response to recent TAG recommendations, including drug treatments covered by NICE Technology Appraisals, are included in Appendix 1. Page 2

4. Implications/Risks Quality If the CCG does not adopt the recommendations of the TAG without good reason, it could limit the treatment choices of the patients it serves and risk lower quality of care. Financial If the CCG does not adopt the recommendations of the TAG without good reason, it may incur unnecessary additional cost for the local health service and risk unnecessary financial pressures. It is expected that any increase in costs will be managed within existing resources; although some recommendations can generate cost efficiencies over existing care, some will create potential cost pressures for the CCG. Constitutional and Legal There is also the risk of legal challenge if any treatment recommended by a NICE Technology Appraisal is considered by an appropriate health clinician to be best NHS treatment option of those clinically indicated for the patient but that treatment is not commissioned by the CCG. Equality and Diversity None. 5. Conclusions By considering and approving the recommendations identified in Appendix 1, the CCG will be clarifying its commissioning positions on the identified treatments. This will support the CCG and its commissioned providers to offer quality treatment to its population consistent with best use of NHS resources and to ensure statutory requirements of the CCG are met with regards to NICE Technology Appraisals. 6. Recommendation The Governing Body is asked to: 1. Note and formally approve the TAG recommendations Authors: Titles: Dr Mark Duggleby and Ken Latta CCG Prescribing Lead and CSU Lead Strategic Pharmacist Page 3

HRW CCG Decisions following consideration of TAG recommendations Treatment Advisory Group Policy Recommendations: Treatment Tocilizumab 162 mg solution in pre-filled syringe (for subcutaneous injection) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have either responded inadequately to, or who were intolerant to, previous therapy with one or more disease-modifying antirheumatic drugs (DMARDs) or tumour necrosis factor (TNF) antagonists. Commissioning Recommendation from TAG Tocilizumab s/c injection is a treatment option for rheumatoid arthritis patients in line with NICE TA 247 (in combination with methotrexate). Points which were considered The SUMMACTA study demonstrated the non inferiority (not better not worse) of tocilizumab s/c against the tocilizumab IV formulation. In the SUMMACTA study, the proportions of all adverse events (AEs) and serious adverse events (SAEs) were similar between the two treatment groups. Injection site reactions were reported more frequently with tocilizumab SC (n=64; 10%) than tocilizumab IV (n=15; 2.4%). The most common symptoms associated with injection site reaction were erythema, pain, pruritis and haematoma. The s/c route for tocilizumab injection allows this drug to be supplied through a homecare provider, which would save on VAT as well as offer a more convenient administration option for patients as it does not require monthly visits to hospital for treatment. This product is also subject to a discounted patient access scheme which means the price is increasingly competitive compared with SC anti TNFs Service delivery costs will decrease as patients will no longer come to hospital for a monthly infusion but there will be a homecare delivery charge. Tocilizumab is supported by NICE as a first, second or third line biologic in the present rheumatoid arthritis pathway. The patent for tocilizumab is not known at this time, however biosimilar molecules would be expected in the future. Annual cost comparison between the IV and SC tocilizumab: IV tocilizumab SC tocilizumab through homecare provider Drug cost 11,182.08 (inc VAT) 9318.40 # Delivery costs 13 day case attendences* 4 x homecare deliveries* Response by HRW CCG Support TAG recommendation to routinely commission as a treatment option. It would be prescribed and managed by secondary care specialists as a hospital only drug. # Ref: London Medicines Evaluation Network Review - tocilizumab subcutaneous injection for rheumatoid arthritis. September 2014 (includes PAS discount) NB this information is already in the public domain. * These costs are likely to vary between different acute hospital trusts. Topical alprostadil cream (Vitaros ) for the treatment of men 18 years of age with erectile dysfunction (ED) Alprostadil cream is recommended as an option after PDE-5 inhibitors e.g. sildenafil or where PDE-5 inhibitors are contraindicated in adult males with erectile dysfunction who meet the criteria listed in part XVIIIB of the NHS Drug Tariff. In two randomised controlled trials, alprostadil 300mcg cream statistically improved erectile function and intercourse ability compared with placebo but the average absolute benefit was modest and only 31%-40% of men (depending on outcome considered) obtained a clinically relevant response. It is not known how topical alprostadil cream compares to other ED therapies. According to the European guidelines, efficacy (erection rigidity sufficient for vaginal penetration) is seen in 56%-84% with PDE5 inhibitors (depending on drug and dose), up to 90% of men using vacuum erection devices, more than 70% of men using intracavernosal alprostadil and 30-66% of men using intraurethral alprostadil. European guidelines on ED advise that alprostadil offers an alternative choice for men who cannot tolerate or have contraindications to PDE5 inhibitors or in whom they are ineffective. The SPC states that the onset of erection is within 5 to 30 minutes. Improvement of erections will last for about 1 to 2 hours. Each patient should be instructed on proper technique for administration prior to self-administration. The cream has similar contraindications, cautions Support TAG recommendation to routinely commission as a treatment option. It could be prescribed in 4

and interactions to other alprostadil formulations e.g. unstable CV disease, previous MI, orthostatic hypotension or predisposition to primary care. priapism. Concomitant administration with other ED agents is not recommended. The topical application route may be preferred to the intraurethral or antracavernosal route by some men. The commonly reported adverse events are transient, localised urogenital effects including penile burning, pain and erythema in men, and vaginal burning and vaginitis in female partners. The maximum frequency of use is no more than 2-3 times per week and only once per 24-hour period. Alprostadil for erectile dysfunction may only be prescribed on the NHS in men who meet the criteria listed in part XVIIIB of the Drug Tariff. Alprostadil cream costs 10 per dose, which is significantly more than generic sildenafil but slightly less costly than other alprostadil products at usual therapeutic dose. Advice regarding the quantity of medication to prescribe remains unchanged from that outlined in Health Service Circular HSC 1999/148, which recommends one treatment per week at NHS expense, based on research evidence in the 40-60 year age group, but does allow GPs to use their clinical judgement to prescribe more than one treatment per week. Similar guidance may wish to be considered with this product. Prescribing data for alprostadil products for the time period of January 14 December 14 Drug Items Cost Alprostadil cavenosal injection (Caverject) 80 5,600.65 Alprostadil cavenosal injection (Viridal) 23 805.96 Alprostadil urethral application (Muse) 126 9,000.72 Alprostadil cream (Vitaros) 5 221.85 5

NICE Medicines Update: 2 Nice Guidance Background Cost Implications Points to consider Response of HRW CCG TA 336: Empagliflozin in combination therapy for treating type 2 diabetes Empagliflozin in a dual therapy regimen in combination with metformin is recommended as an option for treating type 2 diabetes, only if: a sulfonylurea is contraindicated or not tolerated, or the person is at significant risk of hypoglycaemia or its consequences. Empagliflozin in a triple therapy regimen is recommended as an option for treating type 2 diabetes in combination with: metformin and a sulfonylurea or metformin and a thiazolidinedione. Empagliflozin in combination with insulin with or without other antidiabetic drugs is recommended as an option for treating type 2 diabetes. People currently receiving treatment initiated within the NHS with empagliflozin that is not recommended for them by NICE in this guidance should be able to continue treatment until they and their NHS clinician consider it appropriate to stop. TA 335: Rivaroxaban for preventing adverse outcomes after acute management of acute coronary syndrome. Rivaroxaban is recommended as an option within its marketing authorisation, in combination with aspirin plus clopidogrel or aspirin alone, for preventing atherothrombotic events in people who have had an acute coronary syndrome with elevated cardiac biomarkers. Clinicians should carefully assess the person's risk of bleeding before treatment with rivaroxaban is started. The decision to start Empagliflozin (Jardiance by Boehringer Ingelheim) is an orally administered selective sodium-glucose cotransporter-2 (SGLT-2) inhibitor, which lowers blood glucose in people with type 2 diabetes by blocking the reabsorption of glucose in the kidneys and promoting excretion of excess glucose in the urine. The recommended starting dosage is 10 mg once daily for both monotherapy and as an add-on combination therapy with other glucose-lowering medicinal products including insulin. According to the summary of product characteristics, the dosage can be increased to a maximum of 25 mg daily for people who tolerate empagliflozin well and need tighter glycaemic control, if they have an estimated glomerular filtration rate (egfr) of 60 ml/min/1.73 m 2 or more. The cost of empagliflozin is 36.59 (excluding VAT) per pack of 28 tablets for both 10 mg and 25 mg doses (MIMS December 2014). The annual cost of empagliflozin is estimated to be 477.30. Rivaroxaban (Xarelto by Bayer), co-administered with aspirin alone or with aspirin plus clopidogrel or ticlopidine, is indicated for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome with elevated cardiac biomarkers. The licenced dose is 2.5 mg twice daily. Patients should also take a daily dose of 75 100 mg aspirin or a daily dose of 75 100 mg aspirin in addition to either a daily dose of 75 mg clopidogrel or a standard daily dose of ticlopidine. Treatment with rivaroxaban should be evaluated regularly in the individual patient, weighing the risk for ischaemic events against the bleeding risks. Extension of treatment beyond 12 months should be done on an individual patient basis because experience up to 24 months is limited. Treatment The guidance is not expected to have a significant impact on NHS resources. Empagliflozin provides an additional treatment option for people with type 2 diabetes alongside other treatment options which have similar costs and outcomes. The annual cost associated with implementing the guidance is estimated as 16,100 per 100,000 population, based on the standard assumptions in the template. It should be noted that the template assumes that 99% of the admissions with STEMI and NSTEMI eligible for secondary prevention of atherothrombotic events currently have aspirin plus clopidogrel. It should be noted that this is likely to be an overestimate as local guidelines would recommend ticagrelor in combination with aspirin for the majority of patients Empagliflozin is one of three SGLT-2 inhibitors, the other two are dapagliflozin and canagliflozin both of which have been approved by NICE. NICE recommendations for empagliflozin are the same as canagliflozin but dapaglifozin is only recommended for dual therapy in combination with metformin or with insulin. Cost comparison Treatment Strength Annual drug Cost Empagliflozin 10mg or 25mg 477.30 Canagliflozin100mg/ 300mg 477.26/ 608.22 Dapagliflozin 10mg 477.30 Sitagliptin 100mg 433.86 Local decision making groups will need to approve as a treatment option in line with NICE guidance. Rivaroxaban 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone reduced the composite risk of myocardial infarction, stroke and death from cardiovascular causes by 20% compared with aspirin plus clopidogrel or with aspirin alone. Treatment with rivaroxaban resulted in more non-cabg-related major bleeding than aspirin plus clopidogrel or aspirin alone. In England, treatment options for people with ST segment elevation myocardial infarction (STEMI) include percutaneous coronary intervention followed by dual antiplatelet therapy, prasugrel in combination with aspirin Accept NICE recommenda tion as a treatment option. Accept NICE recommenda tion as a treatment option. 6

treatment should be made after an informed discussion between the clinician and the patient about the benefits and risks of rivaroxaban in combination with aspirin plus clopidogrel or with aspirin alone, compared with aspirin plus clopidogrel or aspirin alone. A decision on continuation of treatment should be taken no later than 12 months after starting treatment. Clinicians should regularly reassess the relative benefits and risks of continuing treatment with rivaroxaban and discuss them with the patient. TA 337: Rifaximin for preventing episodes of overt hepatic encephalopathy Rifaximin is recommended, within its marketing authorisation, as an option for reducing the recurrence of episodes of overt hepatic encephalopathy in people aged 18 years or older. with rivaroxaban should be started as soon as possible after stabilisation of the acute coronary syndrome event (including revascularisation procedures); at the earliest 24 hours after admission to hospital and at the time when parenteral anticoagulation therapy would normally be discontinued. The list price of rivaroxaban 2.5 mg is 58.88 per 56 capsule pack (excluding VAT, company submission). The recommended dose is 2.5 mg twice daily, which equates to a price of 2.10 per day. Total acquisition costs depend on the duration of therapy. Assuming a treatment duration of 12 months, total acquisition costs are 766.50. Costs may vary in different settings because of negotiated procurement discounts. Rifaximin (Targaxan by Norgine) is a semi-synthetic derivative of the antibiotic rifamycin. Rifaximin decreases intestinal production and absorption of ammonia, which is thought to be responsible for the neurocognitive symptoms of hepatic encephalopathy, thereby delaying the recurrence of acute episodes. Rifaximin has a marketing authorisation in the UK 'for the reduction in recurrence of episodes of overt hepatic encephalopathy in patients aged 18 years or older'. The summary of product characteristics highlights that 91% of people in the pivotal study were using concomitant lactulose. The summary of product characteristics lists the following common adverse reactions for rifaximin: depression, dizziness, headache, dyspnoea (shortness of breath), upper abdominal pain, abdominal distension, diarrhoea, nausea, vomiting, ascites (accumulation of fluid in the abdominal cavity), rashes, pruritus (itching), muscle spasms, arthralgia (joint pain), and peripheral oedema (swelling). Rifaximin is available as 550 mg film-coated tablets at a net price of 259.23 per 56-tablet pack (excluding VAT; British national formulary online [accessed December 2014]). It is administered orally at a recommended dose of 550 mg twice daily. The company estimated an average cost of 1689.65 for 6 months of treatment. admitted with NSTEMI and STEMI. Estimated total CCG cost of treatment over 3 years Year 1 = 36,952 Year 2 = 44, 342 Year 3 = 52,091 The above figures were calculated using the NICE costing template using the following assumptions: -The prevalence of cirrhosis was estimated to be 76 per 100,000 population. -Evidence suggests that overt hepatic encephalopathy occurs in 37.5% of people with cirrhosis. -91% of patients presenting with overt hepatic encephalopathy are treated with lactulose and at the moment no patients are treated with rifaximin. -The manufacturer estimates the number of people taking rifaximin will rise to 40% of the treated population by year 3. (for those who have undergone percutaneous coronary intervention or in whom it is planned), ticagrelor in combination with low-dose aspirin, or clopidogrel in combination with low-dose aspirin. Previous local network cardiac network guidelines recommended ticagrelor and aspirin first line for the majority of patients admitted with NSTEMI and STEMI. There is no evidence comparing rivaroxaban with ticagrelor or prasugrel for this indication. Regional cardiac network plan to provide guidance relating to the place of rivaroxaban in the present ACS treatment pathway. Local decision making groups may wish to await this guidance before approving it. Standard treatment for prevention of encephalopathy tends to be lactulose but generally at much higher doses, which can result in significant side effects and poor compliance. Neomycin is rarely used now due to risk of renal toxicity. Rifaximin was the only licensed treatment available to prevent episodes of hepatic encephalopathy. This treatment is unlikely to replace lactulose in practice but would be used in combination in the majority of patients. Expert clinical opinion suggests that rifaximin is effective in reducing the recurrence of hepatic encephalopathy episodes and is well tolerated. Treatment with rifaximin may improve quality of life, prevent readmissions to hospital and reduce morbidity and carer burden. Annual cost of rifaximin per patient per year is 3,370. Accept NICE recommenda tion as a treatment option. 7