Standard Versus High Dose Inactivated Influenza Vaccine in RA

Phase 4

Completed

Conditions: Rheumatoid Arthritis

Interventions: Biological: SD-QIV
Biological: HD-TIV

Registration Number: NCT02936180

Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Brief Summary: 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).

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 279

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard dose influenza vaccine	SD-QIV	Patients will receive one dose of FLUZONE® Standard Dose Quadrivalent Inactivated Influenza Vaccine (SD-QIV)
High dose influenza vaccine	HD-TIV	Patients will receive one dose of FLUZONE® High Dose Trivalent Inactivated Influenza Vaccine (HD-TIV)

Primary Outcome Measures

Name	Time	Method
Seroconversion Rate to HD- Versus SD-IV in People With RA	Day 28	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.
Seroprotection Rate to HD- Versus SD-IV in People With RA	Day 28	Seroprotection rate (SPR): the proportion of subjects in a given treatment group attaining a reciprocal HI titre of ≥1:40 at D28 post-vaccination.
Geometric Mean Titres (GMTs) of HI in People With RA Who Received HD- Versus SD-IV	Day 28	Geometric mean titres (GMTs) of HI at D28.

Secondary Outcome Measures

Name	Time	Method
Rates of Side Effects During the Surveillance Period in SD- and HD-IV.	Day 28	Number of Participants with Side Effects
Durability of Detectable Levels of HI Antibody for SD- and HD- IV.	Day 186	Number of participants with detectable HI antibodies at Day 186