Following approval of Eculizumab

Obtaining Eculizumab

Following approval of eculizumab, you will need to liaise with your hospital pharmacist to obtain eculizumab.

At present there are three brands of eculizumab licensed for use in aHUS: Bekemv® (made by Amgen), Epysqli® (made by Samsung Bioepis) and Soliris® (made by Alexion).

Each company has processes to allow you obtain eculizumab for urgent use to allow dosing within 24 hours of approval. Read below for details as to how to obtain a specific brand of eculizumab urgently. This will include access to a specific certificate of vaccination for each company.

In case you have a patient pre-approved for eculizumab at time of transplant:

If your patient has been pre-approved for eculizumab and is planned to have a living donor transplant – you should also follow the processes below.

If your patient has been pre-approved for eculizumab and is planned to have a deceased donor transplant – please go to the following page – Prophylactic use of Eculizumab in patients with aHUS at time of renal transplantation

Bekemv® (made by Amgen)

Biosimilar eculizumab (Note: NOT licensed for use in children under 2 years old)

You will need to complete a Certificate of Vaccination. AMGEN have generated guidance on how to complete the certificate and specific information on Bekemv®. The order form for urgent request of Bekemv® can be found here.

Epysqli® (made by Samsung Bioepis)

Biosimilar eculizumab (licensed for any age)

You will need to complete a specific Certificate of Vaccination and order Epysqli® using this form.

Soliris® (made by Alexion)

Originator eculizumab (licensed for any age)

Instructions to order Soliris® urgently, including access to the certificate of vaccination can be found here.

Reducing Meningococcal Risk

Vaccination against meningococcal disease.

All patients must be vaccinated against meningococcal infections using the vaccines MenACWY and Bexsero at least two weeks prior to receiving/initiating treatment with eculizumab or ravulizumab unless the risk of delaying eculizumab/ravulizumab therapy outweighs the risk of developing a meningococcal infection.

Bear in mind, some patients including some children will have received all/part of the meningococcal vaccines required so a vaccination history should be obtained from the GP.

Antibiotic prophylaxis

We recommend prophylactic antibiotic use and patient vigilance to possible symptoms of meningococcal infection for the duration of eculizumab /ravulizumab treatment.

Meningococcal Titres

As part of the monitoring of serological response, we recommend annual testing of CWY titres. Note – due to the nature of the assay, B-titres cannot be tested whilst patients are receiving eculizumab/ravulizumab. Our specialist aHUS nurses will be in touch to confirm the timing of these titres, and facilitate the process for patients in England. This will include sending out packs comprising pre-paid packaging, blood bottles and the appropriate sample request form. These tests are paid for by NHS England as part of the follow-up of patients receiving eculizumab/ravulizumab within the National aHUS Service.  If you have a patient from outside of England, we would be happy to discuss.

Risk of meningococcal infection and vaccination protocol

Full advice on reducing the risk of meningococcal infection and vaccination protocol is available here (adults / paediatrics).

Certificate of vaccination

A certificate of vaccination needs to be completed to obtain eculizumab (or ravulizumab). Please see sections on ordering drug for links to product specific certificate of vaccinations.

Dosing of Eculizumab

The dose of Eculizumab for induction and maintenance is fixed for adults. For children and adolescents dose the dose is adjusted according to body weight. Complete details of dosing schedules are available at: https://bnf.nice.org.uk/drugs/eculizumab/ and https://bnfc.nice.org.uk/drugs/eculizumab/ and summarised below.

Dosing of Eculizumab

Adult dosing schedule (via 25 - 45 minute IV infusion)

Paediatric dosing schedule (via 1-4 hours IV infusion) - Patient body weight 40kg or more

Paediatric dosing schedule (via 1-4 hours IV infusion) - Patient body weight 30kg to less than 40kg

Paediatric dosing schedule (via 1-4 hours IV infusion) - patient body weight 20kg to less than 30kg

Paediatric dosing schedule (via 1-4 hours IV infusion) - patient body weight 10kg to less than 20kg

Paediatric dosing schedule (via 1-4 hours IV infusion) - patient body weight 5kg to less than 10kg

INITIAL DOSES

900 mg every week for first 4 weeks

Dose as per adult schedule

600 mg every week for first 2 weeks

600 mg first week only

300 mg first week only

MAINTENANCE DOSE

1200 mg at week 5 then 1200 mg every 14 days

Dose as per adult schedule

900 mg at week 3 then 900 mg every 14 days

600 mg at week 3 then 600 mg every 14 days

300 mg at week 2 then 300 mg every 14 days

300 mg at week 2 then 300 mg every 21 days

Adverse Event Reporting

All adverse events in patients receiving eculizumab and ravulizumab must be reported through the Yellow Card scheme, the drug manufacturer Alexion UK  (uk.adverseevents@alexion.com)  and the National aHUS service.

Details of treatment associated adverse events other than meningococcal disease are available:

Eculizumab https://www.medicines.org.uk/EMC/medicine/19966/SPC/Soliris/

Ravulizumab: (emc) (medicines.org.uk)

Summary of Recommendations for Reducing Meningococcal Risk

The greatest known risk to patients receiving eculizumab / ravulizumab is meningococcal infection. To help mitigate this risk, the National aHUS Service recommends the following when commencing eculizumab / ravulizumab

1)  All patients receiving eculizumab / ravulizumab should be vaccinated with both a quadrivalent A, C, W and Y conjugated vaccine and the multi component serogroup B vaccine Bexsero. In addition we recommend that all patients should receive prophylactic antibiotics as soon as they start eculizumab / ravulizumab which they should remain on as long as they are on eculizumab / ravulizumab (and for 4 weeks following cessation of eculizumab or for 16 weeks following cessation of ravulizumab). We would recommend long-term prophylactic penicillin (Pencillin V) or erythromycin (if penicillin allergic).
2) Antibody titres should be tested at 4-6 weeks post-vaccination, and annually whilst on eculizumab / ravulizumab. A serum sample should be sent to the Meningococcal Reference Unit, UK Health Security Agency (formerly PHE) for meningococcal B*, C, W and Y serum bactericidal antibody. Local microbiology laboratories will be able to organise this. [NB For patients under the shared care of the National aHUS Service, this form can be used (for patients on eculizumab/ravulizumab)

Patients with a sub-optimal response should be re-vaccinated (please refer to our adult and paediatric vaccination guideline for more information regarding this, or contact the aHUS Specialist Nurses for advice: ahus.nurses@nhs.net).

*Eculizumab/ ravulizumab interferes with measurement of B titres as it relies on a complement haemolytic assay. As a result, measurement of anti-B titres cannot be interpreted once eculizumab / ravulizumab has been commenced. Measurement of B titres in a patient receiving eculizumab / ravulizumab is not helpful and is therefore not required. However, in patients not currently on eculizumab / ravulizumab such as those patients awaiting eculizumab pre-emptively ahead of renal transplantation, measurement of B titres should be performed as part of the post-vaccination protocol or annual titre measurement when activated onto the transplant list.

3) No further vaccination should be given if a sub-optimal response is seen after 2 doses of vaccine.

4) In responders, antibody titres should be measured at yearly intervals following initial vaccination, and revaccinated if titres fall (see adult and paediatric vaccination guideline for more details).
5) Patients should continue with prophylactic antibiotics whilst on eculizumab / ravulizumab.
6) Patients with aHUS should be vaccinated when they are listed for transplantation and antibody titres checked at 4-6 weeks post-vaccination, and yearly thereafter.

Full guidelines on the prevention of meningococcal disease in aHUS patients receiving eculizumab / ravulizumab are available for  adult/children

Blueteq and Shared Care

Blueteq is the system that NHS England introduced to approve payment of high cost drugs.

We are able to authorise patients to receive eculizumab or ravulizumab on blueteq following agreement for ongoing shared care between the National aHUS Service and the local teams.

For a patient newly started on eculizumab or ravulizumab,

We (National aHUS Service) will complete the specialist centre form once we have confirmation of shared care via return of a signed shared care protocol

There is a form to complete at your end (referring team) – your pharmacists will likely be very familiar with this system and will probably fill this out for you if they are made aware

Complement blockade monitoring

Testing for evidence of complement blockade by CH50 and AP100 and soluble C5b-9 is recommended when a patient has commenced complement inhibition.

For patients commencing eculizumab:

Samples should be sent for monitoring once patients are stable on eculizumab: (pre-3rd dose at 1200mg for adults, and variable for children according to weight). The aHUS Specialist Nurses will liaise with the local team to inform them on a case-by-case basis when these bloods are due (Both for adult and paediatric patients).

For patients commencing ravulizumab:

Samples should be sent for monitoring once patients are stable on ravulizumab:
For patients over 20kg, these should be taken prior to the 18 week dose
For patients under 20kg, these should be taken prior to the 10 week dose

Additional samples may be required and will be discussed with the referring consultant on a case-by-case basis. These may be the case if results are indeterminate or if they necessitate a change in dose. We may also recommend further sampling if we have been notified of clinical concern about the patient or in the case of patients who have commenced eculizumab pre-emptively at time of transplantation.

Samples should be sent as instructed on our follow up aHUS bloods form (on eculizumab / ravulizumab)

General monitoring of laboratory parameters

The following are useful to monitor patients with aHUS. The frequency will depend on the clinical picture.

Renal function
Full blood count
Lactate dehydrogenase
Haptoglobin
Urinalysis
Urine Protein/Creatinine ratio

Anti-factor H autoantibody monitoring

We recommend 6-monthly monitoring of patients who have anti-factor H autoantibodies detected on screening.

The aHUS Specialist Nurses will co-ordinate this by liaising with patients and local teams. These samples need to be sent to Newcastle using this form.

The aHUS Specialist Nurses are responsible for feeding back results when they are available to the NRCTC managing consultant as well as the local clinician (and their patients). Results will be fed back by letter with an interpretation of the results. If anti-factor H antibodies are consistently no longer detected, we will discuss the appropriateness of stopping eculizumab with patients and local teams.

A period of monitoring and counselling about risk of relapse should follow if eculizumab is stopped – Monitoring protocol for patients stopping eculizumab

We will also continue to monitor anti-FH antibodies after eculizumab has been stopped [6 monthly for 2 years, annually thereafter].

Home administration of eculizumab/Ravulizumab

Home administration of Eculizumab / Ravulizumab can be provided by various homecare companies. This service is funded by Alexion Pharma UK and is available for both paediatric and adult patients including those with access systems such as a port-a-cath.

Our specialist nurses can provide details of who to contact for these services so that the local clinical team can set this up.

More information

Switching patients from Eculizumab to ravulizumab

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