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A Systematic Review and Meta-Analysis of Anti-Rheumatic Drugs and Vaccine Immunogenicity in Rheumatoid Arthritis

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)733-744
JournalJournal of Rheumatology
Issue number6
Early online date1 Jun 2018
Accepted/In press15 Dec 2017
E-pub ahead of print1 Jun 2018
Published1 Jun 2018


King's Authors


Objectives: Vaccination is a key strategy to reduce infection risk in RA patients and is advocated in internationally recognised rheumatology society guidelines. The aim was to evaluate to the impact of anti-rheumatic drugs on influenza and pneumococcal vaccine immunogenicity.
Methods: We conducted a systematic literature review and meta-analysis comparing the humoral response to influenza (pandemic and seasonal trivalent subunit
vaccines) and pneumococcal (PPV23, PCV-7, PCV-13) vaccination in adult RA patients treated with anti-rheumatic drugs. Vaccine immunogenicity was assessed by
seroprotection rates measured 3 to 6-weeks post immunisation. Risk ratios and 95% CIs were pooled.
Results: Nine studies were included in the meta-analysis (7 studies investigating anti-rheumatic drug exposures and influenza humoral response, 2 studies
investigating pneumococcal vaccine response). Influenza vaccine responses to all subunit strains (H1N1, H3N2, B strain) were preserved with methotrexate and TNF
inhibitor drug exposure. Methotrexate but not TNF inhibitor drug exposure was associated with reduced 6B and 23F serotype pneumococcal vaccine response (risk
ratio 0.42, 95% CI 0.28 to 0.63) vs. 0.98 (95% CI 0.58 to 1,67)), however limited data were available to draw any firm conclusions. Combination of methotrexate with
tocilizumab or tofacitinib was associated with reduced pneumococcal and influenza vaccine responses.
Conclusions: Anti-rheumatic drugs may negatively impact humoral responses to vaccination as evidenced by pneumococcal responses with methotrexate exposure,
however they are safe and should not preclude immunisation against vaccine preventable disease. Vaccination should be considered in all RA patients and
encouraged as part of routine care. Systematic review registration number: PROSPERO 2016: CRD42016048093.

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