Standard Versus High Dose Inactivated Influenza Vaccine in RA

Study Overview
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Brief Summary
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Influenza, a vaccine-preventable respiratory disease, is ranked 8th among the causes of death in the Canadian population. Among rheumatoid arthritis (RA) patients, the incidence of both seasonal influenza and serious influenza-related illness (IRI) are increased. Despite being a high priority group targeted for vaccination, the diagnosis of RA and other patient-specific factors (i.e. older age, treatment, current smoking) are linked to impaired vaccination responses. Thus the burden of influenza among people with RA is disproportionally high, and interventions to improve responses to influenza vaccination are urgently needed. Strategies to optimize protection in another vulnerable group, the elderly, include the use of quadrivalent vaccines, higher antigen doses, and adjuvants. A high-dose, trivalent, inactivated influenza vaccine (HD-TIV) has recently been shown to have a similar safety profile to standard dose vaccine (SD-TIV) with improved immunogenicity and protection in adults ≥65 years of age. Whether or not analogous strategies to improve responses to influenza vaccine will enhance protection in people with RA is unknown. The investigators hypothesize that the use of the HD-influenza vaccine will improve vaccine-induced protection (i.e. seroconversion and seroprotection) in people with RA compared to SD-influenza vaccine. The investigators propose to conduct a stratified, randomized, modified double blind, active-controlled trial to assess immune responses to two commercial influenza vaccines containing different antigen doses in individuals with RA.

Official Title
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Improving Influenza Immunization Responses in Rheumatoid Arthritis: A Strategy To Enhance Protection Against A Preventable Cause Of Death In An At Risk Population?

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: HD-TIV
* Biological: SD-QIV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of seropositive RA (rheumatoid factor (RF) and/or anti-CCP antibody positive) based on the 2010 ACR-EULAR criteria. At least 6 months of treatment including anti-TNF agents, abatacept, rituximab (dose received within the previous 6 months) and/or methotrexate. Informed consent form signed and dated. Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: Vaccination against influenza in the 6 months preceding the trial vaccination. Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to TIV or to a vaccine containing any of the same substances. History of Guillain-Barré syndrome within six weeks of a previous influenza vaccination. Dementia or any other cognitive condition that could interfere with the trial procedures. Thrombocytopenia or bleeding disorder contraindicating IM vaccination (according to treating rheumatologist). Current alcohol abuse or drug addiction. Moderate or severe acute illness with or without fever. If this exists, vaccination will be deferred until the individual has been medically stable and/or afebrile for at least 24 hours. Signs and symptoms of an acute infectious respiratory illness. If this exists, vaccination will be deferred until the symptoms resolve. Pregnant women (the rationale for excluding this group is not their lack of indication for vaccination but the changes of maternal immune responses during pregnancy)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard dose influenza vaccine<br>Patients will receive one dose of FLUZONE® Standard Dose Quadrivalent Inactivated Influenza Vaccine (SD-QIV) | Biological: SD-QIV<br> <br> |
| Active Comparator: High dose influenza vaccine<br>Patients will receive one dose of FLUZONE® High Dose Trivalent Inactivated Influenza Vaccine (HD-TIV) | Biological: HD-TIV<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate to HD- versus SD-IV in people with RA | Seroconversion rate (SCR): proportion of subjects in a given treatment group (SD- or HD) with either a ≥4-fold increase in reciprocal HI titres between D0 and D28 or a rise of undetectable HI titre (i.e. <1:10) pre-vaccination (D0) to an HI titre of ≥1:40 at D28 post vaccination. | Day 28 | 
| Seroprotection rate to HD- versus SD-IV in people with RA | Seroprotection rate (SPR): the proportion of subjects in a given treatment group attaining a reciprocal HI titre of ≥1:40 at D28 post-vaccination. | Day 28 | 
| Seroconversion factor in people with RA who received HD- versus SD-IV | Seroconversion factor or GMFR: the geometric mean of the ratio of GMTs (D28/ D0). | Day 28 | 
| Geometric mean titres (GMTs) of HI in people with RA who received HD- versus SD-IV | Geometric mean titres (GMTs) of HI at D0 and D28. | Day 0 and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durability of HI antibody responses for SD- and HD- IV. |  | Day 186 | 
| Rates of side effects during the surveillance period in SD- and HD-IV. |  | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, Flu vaccine, Influenza