{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:18:42Z","timestamp":1792718322922,"version":"4.5.0"},"reference-count":22,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National Institute for Health and Care Excellence (NICE) but it remains unclear how vaccine efficacy is impacted by different immunosuppressive agents. Our objective was to compare the chance of a seroconversion following vaccination against pneumococcus in patients with inflammatory arthritis to that in the general population, as well as to compare the chance of seroconversion across different targeted therapies. Methods: We searched MEDLINE, Embase and the Cochrane Library databases from inception until 20 June 2023. We included randomized controlled trials and observational studies. Aggregate data were used to undertake a pairwise meta-analysis. Our primary outcome of interest was vaccine seroconversion. We accepted the definition of serological response reported by the authors of each study. Results: Twenty studies were identified in the systematic review (2807 patients) with ten reporting sufficient data to be included in the meta-analysis (1443 patients). The chance of seroconversion in patients receiving targeted therapies, relative to the general population, was 0.61 (95% CI 0.35 to 1.08). The reduced odds of response were skewed strongly by the effects of abatacept and rituximab with no difference between patients on TNF inhibitors (TNFis) or IL-6 inhibition and healthy controls. Within different inflammatory arthritis populations the findings remained consistent, with rituximab having the strongest negative impact on vaccine response. TNF inhibition monotherapy was associated with a greater chance of vaccine response compared with methotrexate (2.25 (95% CI 1.28 to 3.96)). JAK inhibitor (JAKi) studies were few in number and did not present comparable vaccine response endpoints to include in the meta-analysis. The information available does not suggest any significant detrimental effects of JAKi on vaccine response. Conclusion: This updated meta-analysis confirms that, for most patients with inflammatory arthritis, pneumococcal vaccine can be administered with confidence and that it will achieve comparable seroconversion rates to the healthy population. Patients on rituximab were the group least likely to achieve a response and further research is needed to explore the value of multiple-course pneumococcal vaccination schedules in this population.<\/jats:p>","DOI":"10.3390\/vaccines11111680","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T09:16:21Z","timestamp":1698916581000},"page":"1680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Systematic Review and Meta-Analysis of Anti-Rheumatic Drugs and Pneumococcal Vaccine Immunogenicity in Inflammatory Arthritis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1307-6528","authenticated-orcid":false,"given":"Deepak","family":"Nagra","sequence":"first","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Bechman","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Adas","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijing","family":"Yang","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Alveyn","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujith","family":"Subesinghe","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Allen","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Patel","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Russell","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Cope","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Norton","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Galloway","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Disease, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00296-020-04731-0","article-title":"The global prevalence of rheumatoid arthritis: A meta-analysis based on a systematic review","volume":"41","author":"Almutairi","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e000935","DOI":"10.1136\/rmdopen-2019-000935","article-title":"Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: A US national cohort study","volume":"5","author":"Mehta","year":"2019","journal-title":"RMD Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1136\/annrheumdis-2019-215882","article-title":"2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases","volume":"79","author":"Furer","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1086\/345954","article-title":"Pneumococcal septic arthritis: Review of 190 cases","volume":"36","author":"Ross","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/art.42386","article-title":"2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases","volume":"75","author":"Bass","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Subesinghe, S., Rutherford, A.I., Ibrahim, F., Harris, H., and Galloway, J. (2016). A large two-centre study in to rates of influenza and pneumococcal vaccination and infection burden in rheumatoid arthritis in the UK. BMC Musculoskelet. Disord., 17.","DOI":"10.1186\/s12891-016-1187-4"},{"key":"ref_7","first-page":"g7647","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: Elaboration and explanation","volume":"350","author":"Moher","year":"2015","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/rheumatology\/kei193","article-title":"Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis","volume":"45","author":"Kapetanovic","year":"2006","journal-title":"Rheumatology"},{"key":"ref_10","first-page":"272","article-title":"Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab","volume":"34","author":"Kaine","year":"2007","journal-title":"J. Rheumatol."},{"key":"ref_11","first-page":"952","article-title":"Response to pneumococcal vaccine in patients with early rheumatoid arthritis receiving infliximab plus methotrexate or methotrexate alone","volume":"34","author":"Visvanathan","year":"2007","journal-title":"J. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1002\/art.30580","article-title":"Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors","volume":"63","author":"Kapetanovic","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"648","DOI":"10.3899\/jrheum.130945","article-title":"Vaccine responses in patients with rheumatoid arthritis treated with certolizumab pegol: Results from a single-blind randomized phase IV trial","volume":"41","author":"Kivitz","year":"2014","journal-title":"J. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1136\/annrheumdis-2013-204427","article-title":"Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: Results of a randomised controlled trial (VISARA)","volume":"74","author":"Bingham","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1186\/s13075-015-0863-3","article-title":"Effect of abatacept on the immunogenicity of 23-valent pneumococcal polysaccharide vaccination (PPSV23) in rheumatoid arthritis patients","volume":"17","author":"Migita","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R171","DOI":"10.1186\/ar4358","article-title":"Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis","volume":"15","author":"Saxne","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Garcia Garrido, H.M., Vollaard, A., D\u2019haens, G.R., Spuls, P.I., Bemelman, F.J., Tanck, M.W., de Bree, G.J., Meek, B., Grobusch, M.P., and Goorhuis, A. (2022). Immunogenicity of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Followed by the 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) in Adults with and without Immunosuppressive Therapy. Vaccines, 10.","DOI":"10.3390\/vaccines10050795"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1093\/mr\/roac029","article-title":"Impact of Janus kinase inhibitors on antibody response to 13-valent pneumococcal conjugate vaccine in patients with rheumatoid arthritis","volume":"33","author":"Mori","year":"2023","journal-title":"Mod. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3899\/jrheum.170710","article-title":"A Systematic Review and Metaanalysis of Antirheumatic Drugs and Vaccine Immunogenicity in Rheumatoid Arthritis","volume":"45","author":"Subesinghe","year":"2018","journal-title":"J. Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/S2213-2600(22)00186-2","article-title":"Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): A randomised, open label, superiority trial","volume":"10","author":"Abhishek","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_21","first-page":"1356","article-title":"Pneumococcal vaccine response in psoriatic arthritis patients during treatment with etanercept","volume":"31","author":"Mease","year":"2004","journal-title":"J. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/art.25034","article-title":"Immunization responses in rheumatoid arthritis patients treated with rituximab: Results from a controlled clinical trial","volume":"62","author":"Bingham","year":"2010","journal-title":"Arthritis Rheumatol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/11\/1680\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:16:08Z","timestamp":1760130968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/11\/1680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,2]]},"references-count":22,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["vaccines11111680"],"URL":"https:\/\/doi.org\/10.3390\/vaccines11111680","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,2]]}}}