Title: Influenza and pneumococcal vaccination in adults with common inflammatory conditions treated with immune suppressing drugs: a study of vaccine uptake, clinical effectiveness, vaccine safety, and facilitators and barriers to vaccination.
Funder: Department of Health and Social Care

Abstract: Background Lack of data about vaccine efficacy and concerns about vaccination associated disease flare-ups are barriers to vaccination in immunosuppressed adults with inflammatory diseases. We recently demonstrated the clinical-effectiveness and safety of the inactive influenza vaccine (IIV) in adults with autoimmune rheumatic diseases. However, its clinical-effectiveness and safety in other common inflammatory conditions, and that of pneumococcal vaccine in any common inflammatory condition is not known. Objectives To examine: the uptake of influenza and pneumococcal vaccines in adults with common inflammatory conditions, the association between administration of influenza and pneumococcal vaccines and respiratory infections, death due to respiratory infections, and inflammatory disease flare-up in adults with common inflammatory conditions*, and the barriers and facilitators of vaccination uptake in adults with common inflammatory conditions. *The safety and clinical-effectiveness of IIV in autoimmune rheumatic diseases has been demonstrated and will not be revisited. Methods The project will be delivered in two work packages (WP). WP-1(Database study): Data source: Clinical Practice Research Datalink (CPRD). Incepted in 1987, it is a longitudinal anonymised electronic database containing health records of >14 million UK residents. It contains details of diagnoses, prescriptions, immunisations, and is linked with hospitalization and mortality records. Population: Adults with inflammatory bowel disease or autoimmune rheumatic disease prescribed immune-suppressing medicines. Data analysis: Separate analyses will be performed for influenza and pneumococcal vaccines. Vaccine uptake will be examined in a cross-sectional study and stratified by age, inflammatory disease, and comorbidities. Cox-regression will be used to examine the association between vaccination and primary-care consultation, hospitalization, and death due to prespecified respiratory infections in a propensity score matched cohort study. Association between vaccination and flares of inflammatory bowel disease or autoimmune rheumatic diseases will be ascertained using self-controlled case-series. WP-2(Interview study): Participants with varying engagement with vaccination and reflecting a broad spectrum of diseases, age-ranges, ethnicities and from both genders will be recruited from rheumatology and gastroenterology clinics. Semi-structured interviews will be conducted, transcribed verbatim, anonymised, and analysed using inductive thematic analysis. Analysis will be iterative, occurring concurrently with the interviews to identify data saturation. Timelines: WP-1: CPRD-ISAC approval obtained prior-to study start. Vaccine uptake and effectiveness, and vaccine safety data analysis and write-up completed by months 9 and 13 respectively. WP-2: Interview guide and protocol development (month-1), ethical approval (month-4), site set-up (month-5), interviews and data analysis (months 6-11), manuscript write-up (month-12). Impact and dissemination Results will be published open-access and presented at scientific meetings. We will partner with national patient charities and professional societies to disseminate the findings to patients, public, and healthcare professionals, and for them to modify existing patient education leaflets to include messages around drivers for vaccination and address themes that underpin vaccine hesitancy. A local dissemination event will be held with PPI advisors. We will influence the NICE Indicator Advisory Committee, Department of Health, and NHS England to include vaccinating immunosuppressed adults with inflammatory conditions with the influenza and pneumococcal vaccines in the GP-Quality Outcome Framework. Such policy change is well known to improve vaccine uptake in the UK.

Lay abstract: Approximately one in fifty adults in the UK has an inflammatory condition such as rheumatoid arthritis. They are treated with medicines that suppress the immune-system and increase the risk of flu and pneumonia. Although these infections can be prevented by vaccines, many immune-suppressed people avoid getting vaccinated because there is very-little research showing direct benefit for them and, there is concern that the jabs may cause their condition to flare-up. Our recent research using anonymous information from the treatment of patients in the NHS showed that the flu-jab protects immune-suppressed people with arthritis from flu, pneumonia, dying due to pneumonia, and prevents arthritis flare-ups. However, whether it will protect people with other inflammatory conditions such as inflammatory bowel disease from infections, and whether it can cause a flare-up of their condition is not known. Similarly, whether the pneumonia-jab prevents infection in immune-suppressed people with any common inflammatory condition (i.e. either arthritis or inflammatory bowel disease) and, whether it can cause their condition to flare-up is not known. Our study will answer these questions. In addition, we will find out how many people with inflammatory conditions in the UK are up-to-date with these jabs. Finally, we will understand why only some people with inflammatory conditions get vaccinated. This study is in two parts. Firstly, we will use routinely collected anonymous information from the care of patients in the NHS. The proportion of people who got vaccinated will be calculated. The risk of flu, chest-infection, and death from pneumonia will be compared between those who got and did not get vaccinated. Next, we will compare the risk of inflammatory bowel disease flare-up in the 3-month period after the flu-jab to that in the rest of the year. Similar analysis will be performed for the pneumonia-jab but also including people with arthritis and arthritis flare-ups. In the second part, we will interview approximately 24 people with a range of inflammatory conditions, and varying degrees of engagement with vaccination, to understand why some people get vaccinated while others do not. We will share our findings with patients, healthcare professionals, and policymakers via national patient charities and professional organisations. They will be presented in scientific meetings and published in medical journals. We will work with national charities to modify their patient education materials to include key messages emerging from our study that address reasons for not getting vaccinated. We will work with the NHS and the government to get vaccination for this at-risk group included in the GP-contract as a mandatory activity. This puts additional responsibility on the GP-surgery to promote vaccination, which is well-known to be effective in increasing vaccination uptake. Thus, this study has the potential to prevent infections and save lives.

Research activity codes: 3.4 VACCINES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;INFECTION