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Association between inactivated influenza vaccine and primary care consultations for autoimmune rheumatic disease flares: a self-controlled case series study using data from the Clinical Practice Research Datalink
  1. Georgina Nakafero1,
  2. Matthew J Grainge2,
  3. Puja R Myles2,
  4. Christian D Mallen3,
  5. Weiya Zhang1,
  6. Michael Doherty1,
  7. Jonathan S Nguyen-Van-Tam2,
  8. Abhishek Abhishek1,4
  1. 1 Academic Rheumatology, University of Nottingham, Nottingham, UK
  2. 2 Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
  3. 3 Primary Care Centre Versus Arthritis, Keele University, Keele, UK
  4. 4 Nottingham NIHR Biomedical Research Centre, Nottingham, UK
  1. Correspondence to Dr Georgina Nakafero, Academic Rheumatology, University of Nottingham, Nottingham NG5 1PB, UK; georgina.nakafero{at}


To examine the association between inactivated influenza vaccine (IIV) administration and primary care consultation for joint pain, rheumatoid arthritis (RA) flare, corticosteroid prescription, vasculitis and unexplained fever in people with autoimmune rheumatic diseases (AIRDs).

Methods We undertook within-person comparisons using self-controlled case-series methodology. AIRD cases who received the IIV and had an outcome of interest in the same influenza cycle were ascertained in Clinical Practice Research Datalink. The influenza cycle was partitioned into exposure periods (1–14 days prevaccination and 0–14, 15–30, 31–60 and 61–90 days postvaccination), with the remaining time-period classified as non-exposed. Incidence rate ratios (IRR) and 95% CI for different outcomes were calculated.

Results Data for 14 928 AIRD cases (69% women, 80% with RA) were included. There was no evidence for association between vaccination and primary care consultation for RA flare, corticosteroid prescription, fever or vasculitis. On the contrary, vaccination associated with reduced primary care consultation for joint pain in the subsequent 90 days (IRR 0.91 (95% CI 0.87 to 0.94)).

Conclusion This study found no evidence for a significant association between vaccination and primary care consultation for most surrogates of increased disease activity or vaccine adverse-effects in people with AIRDs. It adds to the accumulating evidence to support influenza vaccination in AIRDs.

  • autoimmune diseases
  • rheumatoid arthritis
  • vaccination

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  • Handling editor Josef S Smolen

  • Contributors AA conceived the idea for the study and all authors planned the study collaboratively. AA, MG and GN developed the analysis plan; data analysis was undertaken by GN and supervised by MG and AA. JSN-V-T and PRM provided influenza specific input and advised on the data analysis plan. CDM provided primary care input. AA together with GN wrote the first draft of the manuscript. All authors reviewed the results and critically reviewed the manuscript for intellectual content. All authors approved the final version of the manuscript.

  • Funding This work was supported by Versus Arthritis (grant number 21297), formerly Arthritis Research UK, and the National Institute of Health Research (NIHR-RP-2014-04-026).

  • Competing interests CDM is funded by the National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care West Midlands, the NIHR School for Primary Care Research and an NIHR Research Professorship in General Practice (NIHR-RP-2014-04-026). JSN-V-T acknowledges funding from the NIHR Biomedical Research Centre (acute respiratory infections), MD and AA acknowledge funding from the NIHR Biomedical Research Centre (musculoskeletal theme) Nottingham. Potential conflicts of interest: JSN-V-T is currently on secondment to the Department of Health and Social Care, England (DHSC). The views expressed in this paper are those of the authors and do not necessarily represent those of the National Health Service, NIHR or DHSC. All other authors have declared no conflicts of interest.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Independent Scientific Advisory Committee (Reference: 16_288R).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data may be obtained from a third party and are not publicly available.

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