Implementation of NICE TA393/394 in a tertiary Lipid Clinic - the first three years experience

• Identify patients eligible for Evolocumab and Alirocumab through a systematic care pathway of medicines optimisation.
• Provide the training, information, support and follow up required to support good medicines adherence with Evolocumab and Alirocumab.
• Monitor the impact of adoption on patients and the service.

NICE published technologies appraisal guidance TA393 and 394 which recommended Evolocumab and Alirocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia in people either with familial hypercholesterolaemia or who are at high or very high risk of CVD and Low density lipoprotein cholesterol (LDL-C) concentrations persistently above the designated thresholds. The NHS is legally obliged to fund and resource medicines and treatments recommended by NICE's technology appraisals guidance (TAG).

Newcastle, North Tyneside and Northumberland locality already had a well-established specialist lipid clinic service where patients who are unable to achieve appropriate lipid lowering targets or could not tolerate prescribed lipid lowering medication are assessed and reviewed and medications optimised. The Lipid clinic is based at the Royal Victoria Infirmary, Newcastle upon Tyne and accepts referrals from primary and secondary care services in the locality as well as elsewhere in the region. The care pathway of the service is underpinned by the FATS7 local guideline. This provided an ideal service in which to adopt the use of these PCSK9i. 

The service began offering these PCSK9i drugs to patients from August 2016. Adoption was supported because the team had already gained experience through taking part in clinical trials using these drugs and so some of the systems and processes required had become familiar however, the team needed to explore how this could be extended to include NHS patients.

Establishing a nurse specialist post.

From their experience of using these medications in the trial, the team recognised that patients would need training and support in how to inject followed by a planned observation of the patient self-administering before a prescription could be made. Once the medications had been prescribed a formalised follow up system for all patients was developed. Initially the service was delivered entirely by the three lipid clinic consultants, supported by a specialist trainee but as the numbers of patients grew, creation of nurse specialist post was identified as the best way to maintain the service in the longer term.

Pending the establishment of the nurse specialist post the consultants who were prescribing the medication were also providing the training in how to self-inject and on-going support for patients, including management of suspected adverse reactions, arranging follow-up blood tests to assess response, review of results and repeat prescribing. A standard schedule of clinic appointments for initiation and follow-up at 6 month intervals was found to be the most efficient means of delivering the service and provided a clear basis for the establishment of the specialist nurse post.

Patient selection

Patients were identified in the already established lipid service which was treating patients referred by GP’s and other hospital specialists from across the region who were failing to meet targets despite receiving lipid lowering therapy or were experiencing unacceptable side effects of lipid lowering treatment. The team developed an eligibility proforma (attached in the patient vignettes) which could be used by clinicians in conjunction with the FATS7 PCSK9 inhibitor pathway to ensure the patient was eligible and also as a record suitable for audit by pharmacists and the CCG (which confirmed the patient’s eligibility for funding for this treatment).

Dispensing

The team were keen to explore whether patients could collect their prescriptions from a pharmacy (the same chain as provided the hospital pharmacy) near to their home to prevent trips to the hospital. Owing to logistical issues with the pharmacy chain this was not possible. In order to prevent additional trips to hospital the team developed the follow up pathway below to ensure that once patients were established on treatment, clinic reviews and prescription collection could be done at the same time

Patient follow up

For their first course of treatment, eligible patients are given a supply of 6 fortnightly injections for 3 months. The first dose is self-injected by the patient in the clinic under supervision during their 30 minute treatment initiation appointment. All patients are then followed up 8-12 weeks after starting treatment. They are given a form and asked to attend for a non-fasting blood test before their penultimate (5^th) injection at 8 weeks. If the results show a satisfactory response (greater than 20% reduction in non-HDL-cholesterol) they are provided with a further 3 months supply to continue until they return to clinic at 6 months and asked to attend for a further non-fasting blood test before their penultimate (5^th) injection at 5 months. At the 15-minute follow-up clinic appointment there is an overall review of their blood results and patient feedback on adherence and taking the medication. If all remains satisfactory a further 6 months of medication is prescribed, and the patient is reviewed in the same way (blood test, usually collected in primary care, 2 weeks before appointment and before last injection) 6 months later.

System data

The proforma provided a systematic was of auditing the service and practice. In the first year 50 patients were offered the medication.

We audited our practice of PCSK9 inhibitor prescribing in the North East of England. Methods: Data was gathered from Newcastle upon Tyne Hospitals (NUTH),City Hospitals Sunderland (CHS), Gateshead Health, Northumbria Healthcare and County Durham and Darlington (CDDFT) trusts since publication of the guidance (Table 1). TA393 and TA394 were used as standards for the audit.. Results: Data was obtained from 103 patients in total from the 5 trusts. In the former group of FH, there was appropriate initiation in 55 (86%) patients. The median non-HDL-C in this group without CVD was 6.7 mmol/L (95% CI 6.4 to 7.2) reduced to 3.6 mmol/L (95% CI 3.1 to 5.5), whereas the median non-HDL-C in FH with CVD was 5.7 mmol/L (95% CI 5.0 to 6.0) reduced to 2.5 mmol/L(95% CI 2.1 to 3.4) following PCSK-9i treatment. The initiation was appropriate in 33/35 (94%) patients with non-FH or mixed hyperlipidemia with evidence of CVD though data was incomplete in 4 patients and PCSK9i therapy achieved a reduction of median non-HDL-C of 5.5 mmol/L (95% CI 5.0 to 6.3) to 2.4 mmol/L (95% CI 2.0 to 3.3). 102/103 patients achieved more than 20% reduction in their pre-treatment non-HDL-C level. One patient initially did well but then had an unexplained secondary loss of response. A history of statin intolerance was documented in 83% of patients, myalgia and hepatic adverse effects being the most frequent reasons given. Only 11 patients (10%) discontinued treatment due to adverse effects, myalgia and joint pains being the most common symptoms.

Implications. PCSK9 inhibitors Alirocumab and Evolocumab are effective and well tolerated in the majority of patients with a history of statin intolerance. In our region, prescribing of PCSK9 inhibitor in Lipid clinics followed NICE TA 393/394 recommendations closely but the number of treatment initiations in high risk non-familial hypercholesterolaemia patients was lower than expected

Clinical case studies

The attached document presents patient case studies showing the impact of these medicines on patients.

Patients are very accepting of this treatment option. They say that is it easy to use the injection devices.

Referral rates of statin intolerant secondary prevention cases is lower than expected suggesting than many eligible patients are not being offered these new therapeutic options.

• Engage with your Area Prescribing Committee to develop an agreed implementation plan for TA393/394 which will be supported by participating organisations within your locality.
• Have a robust system in place which supports the identification of patients not meeting targets and where appropriate implementation of a medicines optimisation process can take place.
• Be aware that audit data suggests that initiations in high risk non-familial hypercholesterolaemia patients was lower than expected reflecting the referral pattern to lipid clinic and resulting case mix.
• Ensure healthcare professionals within a locality are working to the same guidance on lipid lowering management to achieve a consistent approach to care and patient identification.
• Develop a proforma which can be used to support clinician decision making about patients’ eligibility but also a method of communicating and documenting for CCGs and pharmacies your patients’ eligibility for treatment. This can also be used to audit the service.
• Engagement with commissioners.