One in fifty adults have 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. However, many immune-suppressed people avoid getting vaccinated because there is little research showing direct benefit for them and there is concern that vaccines may flare-up their underlying condition.
Our research using information from CPRD showed that the flu-jab protects people with arthritis from flu, pneumonia, death due to pneumonia, and prevents arthritis flare-up. However, whether it will protect people with another common inflammatory condition affecting the tummy (i.e. inflammatory bowel disease), and whether it can cause a flare-up of the tummy problem is unknown. Similarly, whether the pneumonia-jab prevents infection in people with any inflammatory conditions and, whether it can flare-up these conditions is not known. Our study will answer these questions.
We will use anonymous information from CPRD for this study. The risk of flu, chest-infection, and death from pneumonia will be compared between those who got and did not get vaccinated. Separate analysis will be done for the two vaccines. 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, including people with arthritis.
We will share our findings with patients, healthcare professionals, and policymakers. We will work with the NHS to get vaccination for this at-risk group included in the GP-contract as mandatory activity.
Objectives: To examine
• uptake of influenza and pneumococcal vaccines in immunosuppressed adults with inflammatory conditions,
• association between vaccination with influenza and pneumococcal vaccines and respiratory infections, death due to pneumonia, and inflammatory disease flare-up in adults with inflammatory conditions. The safety and clinical-effectiveness of influenza vaccine in autoimmune rheumatic diseases has been demonstrated by us recently and will not be revisited.
Methods:
Data source: Clinical Practice Research Datalink (CPRD)-Gold. 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 hospitalisation and mortality records. Linked Hospital Episode Statistics and Office for National Statistics databases will be used to define hospitalisations and mortality.
Population: Adults with inflammatory bowel disease (IBD) or autoimmune rheumatic disease prescribed immune-suppressing medicines.
Outcomes:
[1] Vaccine uptake: Administration of inactivated influenza vaccine (IIV) in latest influenza cycle, and administration of pneumococcal vaccine previously.
[2] Clinical effectiveness: Primary-care consultation for influenza-like-illness (for IIV only), Lower Respiratory Tract Infection (LRTI) requiring antibiotics, Chronic Obstructive Airway Disease (COPD) exacerbation. Hospitalisation for pneumonia, COPD exacerbation. Death due to pneumonia.
[3] Vaccine safety:
Flare of IBD defined as either primary-care corticosteroid prescription after 4-month gap or hospitalisation for IBD.
Primary-care consultation for (a) joint pain, (b) joint pain with corticosteroid prescription on the same date, and (c) Rheumatoid Arthritis flare.
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, hospitalisation, and death due to respiratory infections in a propensity score matched cohort study. Association between vaccination and flares of IBD or rheumatic diseases will be ascertained using self-controlled case-series.
[1] Vaccine uptake study: Administration of inactivated influenza vaccine in the latest influenza cycle, and pneumococcal vaccine on any previous date.
[2] A. Clinical effectiveness of inactivated influenza vaccine.
Primary outcome: Primary-care diagnosis of influenza-like-illness.
Secondary outcomes:
a. Lower Respiratory Tract Infection (LRTI): Primary-care diagnosis of LRTI with antibiotic prescribed on the same date (6).
b. Chronic Obstructive Airway Disease (COPD) exacerbation: Either primary-care diagnosis of acute COPD exacerbation, or oral prednisolone and oral antibiotic prescriptions occurring on the same date in someone with a previous diagnosis of COPD (45).
c. Hospitalisation for pneumonia, and COPD exacerbation: Defined using International Statistical Classification of Diseases and Related Health Problems (ICD-10) in the inpatient Hospital Episode Statistics dataset.
d. Death including causes: Defined using ICD-10 codes in the Office for National Statistics dataset.
[2]. B. Clinical effectiveness of pneumococcal vaccine
Primary outcome: Hospitalisation for pneumococcal pneumonia.
Secondary outcomes:
a. Hospitalisation for community acquired pneumonia.
b. Hospitalisation for COPD exacerbation as defined above.
c. Primary-care consultation for LRTI as defined above.
d. Primary-care consultation for COPD exacerbation as defined above.
e. Death due to pneumonia.
[3] A. Influenza vaccination and disease flare.
Outcome: Flare of inflammatory bowel disease defined as either a new primary care prescription of corticosteroids after a 4-month gap (51) or hospitalisation for inflammatory bowel disease.
[3] B. Pneumococcal vaccination and disease flare up.
Outcomes: (a) Flare of inflammatory bowel disease defined as either new primary care prescription of corticosteroids after a 4-month gap (51) or hospitalisation for inflammatory bowel disease flare.
(b) Flare of autoimmune rheumatic disease: (a) primary care consultation for joint pain, (b) primary care corticosteroid prescription on the same date as joint pain consultation, (c) primary care consultation for RA flare.
Abhishek Abhishek - Chief Investigator - University of Nottingham
Abhishek Abhishek - Corresponding Applicant - University of Nottingham
Christian Mallen - Collaborator - Keele University
Georgina Nakafero - Collaborator - University of Nottingham
Matthew Grainge - Collaborator - University of Nottingham
Timothy Card - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation