Use in patients taking immunosuppressive medicines
Public Health England’s Immunisation Against Infectious Disease (The Green book) states that immunosuppressed patients, due to disease or treatment are clinically extremely vulnerable and should be vaccinated against COVID-19. Adult household contacts of people with immunosuppression are also considered to be an at risk group eligible for vaccination.
According to the Patient Group Direction for COVID-19 mRNA vaccine BNT162b2 (Pfizer/BioNTech), the Patient Group Direction for COVID-19 Vaccine Comirnaty (Pfizer/BioNTech),the Patient Group Direction for COVID-19 Vaccine AstraZeneca, (ChAdOx1-S [recombinant]) and the Patient Group Direction for COVID-19 Vaccine Moderna there are no groups of potentially immunosuppressed patients that should be excluded from receiving the vaccine based on their treatment or disease alone. It is, however, noted that some immunosuppressed patients may have a suboptimal response to the vaccine and should therefore continue to avoid exposure unless they are advised otherwise by their doctor.
Patients taking immunosuppressive medicines considered a priority for vaccination
The Green Book suggests that patients taking any of the following medicines should be part of the prioritisation process for vaccination:
- immunosuppressive chemotherapy (i.e. regimens containing any “traditional” chemotherapy)
- immunosuppressive therapy following a solid organ transplant
- immunosuppressive or immunomodulating biological therapies such as anti-TNF monoclonal antibodies, alemtuzumab, rituximab, ofatumumab
- protein kinase inhibitors such as imatinib, erlotinib, everolimus
- poly-ADP ribose polymerase (PARP) inhibitors such as niraparib, olaparib, rucaparib
- long-term immunosuppressive medicines for systemic lupus erythematosus, rheumatoid arthritis or psoriasis
- systemic corticosteroids for more than a month at a dose equivalent to prednisolone 20mg daily (any age)
- a steroid sparing medicine such as cyclophosphamide or mycophenolate
Third primary COVID-19 vaccine dose for immunosuppressed patients
Patients who are immunosuppressed due to underlying health conditions or medical treatment may not mount a full immune response to primary COVID-19 vaccination. The Green Book suggests that these patients should be offered a third primary vaccination.
Individuals whose immunosuppression started at least 2 weeks after the second dose of vaccine do not require an additional dose.
The third dose should be given ideally at least 8 weeks after the second dose. The decision on timing of the third dose should be taken by the specialist involved in the care of the patient. In general, vaccines administered during periods of minimum immunosuppression are more likely to generate better responses.
The Green Book provides the criteria for patients who are eligible for a third primary vaccine dose.
Further advice on particular patient groups
Patients scheduled to begin immunosuppressive therapy
Public Health England’s Immunisation Against Infectious Disease (The Green book) states that “patients who are about to receive planned immunosuppressive therapy should be considered for vaccination prior to commencing therapy (ideally at least two weeks before), when their immune system is better able to make a response. Where possible, it would also be preferable for the 2-dose schedule to be completed prior to commencing immunosuppression. This would entail offering the second dose at the recommended minimum for that vaccine (three or four weeks from the first dose) to provide maximum benefit that may not be received if the second dose was given during the period of immunosuppression.”
Patients being treated with immunosuppressive chemotherapy
The UK Chemotherapy Board Organisations has issued guidance on COVID-19 vaccine for patients receiving systematic anti-cancer therapy (SACT) including monoclonal antibodies. It is recommended that all patients receiving SACT should be considered for vaccination. In terms of timing it is suggested that, if relevant, administration should be timed to coincide with when blood counts have maximally recovered but avoided on same day as chemotherapy. It is also noted that thrombocytopenia may be a minor consideration due to the need for an intramuscular injection – they state that a platelet count of >20×109/L would be preferable. It is advised that ideally vaccination should be delayed in patients with neutropenia who are unwell until the neutrophil count has recovered to >1 x109 /L and are well again. Patients with chronic neutropenia should be vaccinated without delay.
It is also stated that medicines such as BCG, mitomycin, gemcitabine given by bladder instillation does not impact on timing of vaccination.
Patients being treated with corticosteroids (oral, intra-articular, intra-muscular or intravenous)
There are some general principles but in each case the benefits and risks should be discussed with the patient to arrive at a shared decision:
- It is safe to have the COVID-19 vaccine alongside steroid exposure, but the patient may not mount such a good immune response.
- Do not delay vaccination for someone who is taking, has received or is soon to receive steroids in any form.
- If additional steroids are required to control inflammatory disease, that may take priority, as a flare can also worsen the risk from COVID-19
- It may be appropriate to delay a non-essential steroid injection, as part of a shared decision, so that the response to the vaccine is more effective. For a patient who is on an elective waiting list for a steroid injection of up to 80mg methylprednisolone or 80mg triamcinolone, the administration of the COVID-19 vaccine is the priority if the vaccine has been offered to the patient and the prevalence of COVID-19 is high. In this scenario, the steroid injection should be deferred by 2 weeks after the vaccine, to enable the patient to mount the best response to the COVID-19 vaccine.
Patients being treated with rituximab
For rheumatology indications
The British Society of Rheumatology advise that:
- Where clinically possible, the COVID-19 vaccine course should be given four weeks or more before rituximab.
- There may be a sub-optimal response to COVID-19 vaccines, especially for people within six months of the last dose of rituximab, or those who must have maintenance treatment due to their underlying clinical condition. BSR acknowledge that there is no evidence to suggest how long after rituximab a patient should delay vaccination with a COVID-19 vaccine, but consensus suggests this should ideally be 4-8 weeks after rituximab if it is ok to defer a COVID-19 vaccine. However this may be dependent on the prevalence of COVID-19 and should be agreed as being acceptable with the patient
- Where clinically appropriate, consideration should be given to using alternative therapies to rituximab, because of the potential that after rituximab there may be sub-optimal response to a COVID-19 vaccine. This should be on a case-by-case basis, balancing the need for rituximab and the suitability of alternative therapies for the relevant clinical situation.
For oncology indications
The UK Chemotherapy Board Organisations has issued guidance on COVID-19 vaccine for patients receiving systematic anti-cancer therapy (SACT). It is stated that patients receiving monoclonal antibodies including rituximab should be considered for vaccination. They state that there are no issues in relation to timing of vaccination when it is being used as a monotherapy provided blood counts are within acceptable range. When used in combination with cytotoxic chemotherapy administration should be coincide with when blood counts have maximally recovered but avoided on same day as chemotherapy.
For patient with multiple sclerosis
The MS Society Medical Advisers have issued a consensus statement on COVID-19 vaccine for patients receiving MS treatments. Their advice is as follows:
There is no reason to believe that glatiramer acetate, teriflunomide, dimethyl fumarate, beta interferons, and natalizumab reduce the efficacy of the vaccines.
For ocrelizumab there may be a sub-optimal response so it may be beneficial to delay the first course of this medicine in order to get the vaccine first. However there is thought to be limited benefit in delaying the second or third course in order to increase vaccine effectiveness. They also advise this approach for patients receiving rituximab for MS.
Fingolomid, ozanimod and siponimod may also reduce the vaccine response but in general it is felt that it would not be advisable to stop treatment in order to increase the immune response.
Alemtuzumab may reduce the vaccine response so it is recommended that vaccination should be delayed for 3 months after an alemtuzumab infusion. A second course of alemtuzumab can be safely delayed by a few months to support scheduling of COVID-19 vaccination.
Cladrabine may reduce the vaccine response so it is recommended that vaccination should be delayed for 3 months after a course of cladrabine. A second course of cladrabine can be safely delayed by a few months to support scheduling of COVID-19 vaccination.
If ocrelizumab, fingolimod, alemtuzumab, or cladribine are being started for the first time it might be preferable to wait until the vaccination course is complete if this is considered clinically appropriate.
- Updated with information from Green Book about immunosuppressed patients and 3rd primary vaccine dose.
- Updated with new link to Comirnaty PGD
- Resources checked and information remains correct.
- Resources checked and information remains correct.
- Added further advice from BSR on timing of vaccination after a dose of rituximab
- Added advice from MS Medical Advisers on vaccination in patients being treated with immunomodulating treatments for multiple sclerosis
- Added updated advice from National Chemotherapy Boards on vaccination in patients receiving bladder instillations
- Added updated advice from National Chemotherapy Boards on vaccination in patients with neutropenia
- Added revised advice from Green Book regarding vaccination regimen in patients scheduled to start immunosuppressive medicines. Added advice from BSR/ARMA on vaccination in patients taking corticosteroids