Standard Versus High Dose Inactivated Influenza Vaccine in RA

McGill University Health Centre/Research Institute of the McGill University Health Centre279 enrolled

Overview

Patients with rheumatoid arthritis have increased risk of seasonal influenza and influenza-related complications but have reduced vaccine immunogenicity. It is unknown whether patients with rheumatoid arthritis would benefit from more immunogenic vaccine formulations. This study investigated the immunogenicity and safety of a high-dose trivalent inactivated influenza vaccine (HD-TIV) in patients with rheumatoid arthritis compared to a standard-dose quadrivalent influenza vaccine (SD-QIV).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

Conditions

Rheumatoid Arthritis

Interventions

HD-TIVBIOLOGICAL

SD-QIVBIOLOGICAL

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Diagnosis of seropositive RA (rheumatoid factor (RF) and/or anti-CCP antibody positive) based on the 2010 ACR-EULAR criteria. 2. At least 6 months of treatment including anti-TNF agents, abatacept, rituximab (dose received within the previous 6 months) and/or methotrexate. 3. Informed consent form signed and dated. 4. Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: 1. Vaccination against influenza in the 6 months preceding the trial vaccination. 2. 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. 3. History of Guillain-Barré syndrome within six weeks of a previous influenza vaccination. 4. Dementia or any other cognitive condition that could interfere with the trial procedures. 5. Thrombocytopenia or bleeding disorder contraindicating IM vaccination (according to treating rheumatologist). 6. Current alcohol abuse or drug addiction. 7. 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. 8. Signs and symptoms of an acute infectious respiratory illness. If this exists, vaccination will be deferred until the symptoms resolve. 9. 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)

Locations (1)

McGill University Health Centre

Montreal, Quebec, Canada

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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 D28.

Time frame: Day 28

Secondary Outcomes

Durability of Detectable Levels of HI Antibody for SD- and HD- IV.

Number of participants with detectable HI antibodies at Day 186

Time frame: Day 186

Rates of Side Effects During the Surveillance Period in SD- and HD-IV.

Number of Participants with Side Effects

Time frame: Day 28

Data from ClinicalTrials.gov

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