Eculizumab and complement inhibitors inhibit the formation of terminal complement, which has a dramatic effect in preventing the symptoms and complications observed in PNH. Terminal complement is not required for combating most infective organisms but is needed to prevent Neisserial infection. Patients treated with eculizumab / complement inhibitors are therefore predisposed to developing infections from the Neisseria group of bacteria. The infection we are therefore most concerned about is that resulting in meningococcal sepsis or meningitis from the bacterium Neisseria meningitidis.
In order to reduce the risk of patients on eculizumab / complement inhibitors developing meningococcal sepsis all patients starting eculizumab / complement inhibitors are vaccinated with 2 vaccines.
- a quadravalent vaccine against the meningococcal strains A,C,W and Y
- a vaccine against serotype B, the commonest serotype observed in the UK.
Patients are also strongly advised to take daily prophylactic antibiotics, either penicillin V 500mg twice daily (or erythromycin 500mg twice daily if allergic to penicillin).
At the end of 2019 it was agreed by the PNH National Service with advice from the UK Meningitis Reference Center to add ‘Rescue’ antibiotics. All patients on eculizumab / complement inhibitor will keep 2 doses of a second antibiotic of ciprofloxacin 500mg as a back-up. This should be taken if feeling unwell, e.g. having a raised temperature (above 38c), and if there is a delay in receiving medical care / advice. This should not replace contacting a healthcare professional for advice and assessment.
As well as this, all patients on eculizumab / complement inhibitors are given a patient safety card to carry with them which both advises them what to do if they become unwell and serves to alert health care professionals that they are at an increased risk of developing meningococcal infection.
Patients are given emergency out-of-hours contact numbers for their PNH Centre. If a patient on eculizumab / complement inhibitor becomes unwell we advise to call for support. They should also have emergency numbers for their local Haematology department.
If a patient with PNH is unwell and develops a temperature it is important that they are reviewed immediately by a healthcare professional. If meningococcal infection is suspected they should be commenced on either a third generation cephalosporin (if not neutropenic) or meropenem (if neutropenic). The PNH team who sees the patient should also be contacted urgently.