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Covid-19 HSE Clinical Guidance and Evidence
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Prof David Kane, National Clinical Programme for Rheumatology
Influenza and Pneumococcal vaccination are recommended for all rheumatology patients receiving immunotherapy and ALL patients being considered for SARS-CoV-2 vaccination should be strongly advised to have Influenza and Pneumococcal vaccinations. There is very good quality evidence of mortality reduction for patients who have influenza and pneumococcal vaccination.
Which groups of Rheumatology patients should be prioritized for SARS-CoV-2 vaccination?
Chapter 5a includes Table 5.2 Medical conditions and medication associated with very high risk or high risk of severe COVID-19 disease.
Recommendations for selection of SARS-CoV-2 vaccine by patient subgroup
The Pfizer Biotech mRNA vaccine and Moderna mRNA vaccines are preferred for patients on immunosuppressives but non-replicating vector vaccines (Astra Zeneca / University of Oxford) are also deemed effective and safe for patients on immunosuppressives.
Recommendations for optimal timing of administration of SARS-COV-2 vaccine
(a) Patients on Methotrexate
Several studies have addressed the optimal timing of Influenza vaccination in rheumatology patients on low dose methotrexate. Patients on methotrexate who held their medication for 2 weeks after administration of influenza vaccination had a 4 fold increase in neutralizing antibody titres without a significant increased risk of disease flare compared to those who did not interrupt their MTX dosing.
It is not known if this translates into reduced influenza infection rates though the supposition that it does is logical based on what we know about vaccines and how they work. For surgery it is already established safe practice to temporarily pause methotrexate and restart at 10-14 days without increased risk of flare. Therefore depending on your patient’s circumstances you may recommend that patients on methotrexate should ideally schedule SARS-CoV-2 vaccination at the end of a treatment cycle and hold treatment for a maximum of 2 weeks if the treating clinician and patient agree on this strategy.
In practice during the 2021 vaccine rollout it has been important not to delay vaccination so we have pragmatically advised patients to not delay vaccination and simply postpone methotrexate afterwards - “skip a scheduled dose of methotrexate due immediately after vaccination”.
There is no evidence that there is a benefit from stopping other treatments.
(b) Patients on Rituximab
Patients on rituximab have reduced numbers of B cells and a poorer antibody generation response to vaccines. It is recommended that patients should have SARS-CoV-2vaccination ideally 4 weeks before they receive rituximab treatment and if on treatment that it be scheduled for the end of a treatment cycle (eg 6 months after last dose for optimal effect).
Furer V, Rondaan C, Heijstek MW et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020; 79: 39-52
Iacobucci G Covid-19: Risk of death more than doubled in people who also had flu, English data show. BMJ. 2020; 370m3720
Hua C, Barnetche T, Combe B, Morel J. Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2014; 66: 1016-1026
Park JK, Lee MA, Lee EY et al. Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2017; 76: 1559-1565
Park JK, Lee YJ, Shin K et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2018; 77: 898-904
Park JK, Kim MJ, Choi Y, Winthrop K, Song YW, Lee EB. Effect of short-term methotrexate discontinuation on rheumatoid arthritis disease activity: post-hoc analysis of two randomized trials. Clin Rheumatol. 2020; 39: 375-379
Gianfrancesco M, Hyrich KL, Al-Adely S et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020; 79: 859-866