key: cord-0743481-qnnqj3cu
authors: Rodziewicz, Mia; Dyball, Sarah; Bruce, Ian; Parker, Ben
title: Pausing drugs and spacing vaccines: an open question
date: 2021-09-22
journal: Lancet Rheumatol
DOI: 10.1016/s2665-9913(21)00274-5
sha: 8c1b54fc7a70aa152b54a068e064e9f5b50ab944
doc_id: 743481
cord_uid: qnnqj3cu

nan

The authors reported that their data implied that successful vaccination of patients with rheumatoid arthritis who are taking DMARDs might depend on an interval of 3-6 weeks between vaccinations, but we propose that a longer interval might be of benefit to some patients. Methotrexate is known to reduce the immunogenicity of influenza and pneumococcal vaccinations, 2 and Haberman and colleagues suggested that this fact might also be true of COVID-19 vaccination in patients with immunemediated inflammatory diseases. 3 It is possible that a short discontinuation of methotrexate might increase the immune response that is induced by COVID-19 vaccination. Indeed, one study of seasonal influenza vaccination in patients with rheumatoid arthritis receiving methotrexate noted that, in people with stable disease (mean Disease Activity Score 28-CRP=2·3 [SD 1·1]), a discontinuation of the drug for 2 weeks after vaccination resulted in greater humoral responses, without a convincing increase in flares (5·1% vs 10·6%; p=0·070) or use of rescue medications (4·5% vs 6·3%; p=0·49). 4 For an interval of 3 weeks between vaccine doses, methotrexate would need to be withheld for a total of 5 weeks. An interval of 12 weeks between doses of COVID-19 vaccine (ie, the recommended maximum interval in the UK) 5 would allow methotrexate to be safely discontinued for 2 weeks after to first dose, resumed for 10 weeks, and discontinued for a further 2 weeks after the second dose before returning to usual therapy. Another option would be the use of a single-dose vaccine, such as the Ad26.COV2.S vaccine (Janssen), which would require a pause in methotrexate therapy for just 2 weeks. In stable patients, this pause might allow optimisation of a vaccine-induced immune response without significant risk of disease flare. The external validity of these data is poor, and further research is required, particularly in patients with organ-threatening diseases (eg, antineutrophil cytoplasmic antibody-associated vasculitis and systemic lupus erythematosus). While we await large studies to support these findings, we suggest temporary methotrexate discontinuation as a pragmatic approach to maximising vaccine effectiveness in patients with a low risk of flare. MR 

Anti-SARS-CoV-2 mRNA vaccine in patients with rheumatoid arthritis

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

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease

Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial

Optimising the COVID-19 vaccination programme for maximum shortterm impact

We thank Mia Rodziewicz and colleagues for their interest in our Comment 1 on the immunogenicity of mRNA-based vaccines against SARS-CoV-2 in patients with rheumatoid arthritis and their discussion regarding the interval between the two vaccine doses. Most of our patients (44 [83%] of 53) received the mRNA-based BNT162b2 (Pfizer-BioNTech) vaccine and nine (17%) patients received the mRNA-1273 vaccine (Moderna); the interval between the first and second dose was 3-6 weeks according to Swiss federal regulations, which were based on the intervals that were proposed by the manufacturers.In contrast to mRNA-based vaccines, the ChAdOx1 nCoV-19 vaccine (AstraZeneca), which is used in the UK, consists of the replication-deficient simian adenovirus vector ChAdOx1 and the full-length structural surface glycoprotein (ie, spike protein) of SARS-CoV-2. To achieve a protective anti-SARS-CoV-2 immune response, two vaccine doses are considered to be necessary. In the case of a vectorbased vaccine, concern exists regarding the use of an early homologous boost, because an anti-vectordirected immune response might interfere with the effectiveness of the second vaccine dose to induce a potent anti-SARS-CoV-2-directed