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. 2014 Jan 2;16(1):R2.
doi: 10.1186/ar4427.

Impact of anti-rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis

Meliha C Kapetanovic, Lars-Erik Kristensen, Tore Saxne, Teodora Aktas, Andreas Mörner, Pierre Geborek

Impact of anti-rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis

Meliha C Kapetanovic et al. Arthritis Res Ther. .

Abstract

Introduction: An adjuvanted pandemic H1N1 influenza (pH1N1) vaccine (Pandemrix) was reported as highly immunogenic resulting in seroconversion in 77 to 94% of adults after administration of a single dose. The aim of the study was to investigate the impact of different anti-rheumatic treatments on antibody response to pH1N1 vaccination in patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA).

Methods: Patients with arthritis (n = 291; mean age 57 years, 64% women) participated. Hemagglutination inhibition (HI) assay was performed on blood samples drawn before and after a mean (SD) of 8.3 (4) months following vaccination. A positive immune response i.e. seroconversion was defined as negative prevaccination serum and postvaccination HI titer ≥40 or a ≥4-fold increase in HI titer. All patients were divided into predefined groups based on diagnosis (RA or SpA) and ongoing treatment: methotrexate (MTX), anti-tumor necrosis factor (anti-TNF) as monotherapy, MTX combined with anti-TNF, other biologics (abatacept, rituximab, tocilizumab) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics. Predictors of positive immune response were studied using logistic regression analysis.

Results: The percentage of patients with positive immune response in the different treatment groups was: 1. RA on MTX 42%; 2. RA on anti-TNF monotherapy 53%; 3. RA on anti-TNF + MTX 43%; 4. RA on other biologics (abatacept 20%, rituximab 10% and tocilizumab 50%); 5. SpA on anti-TNF monotherapy 76%; 6. SpA on anti-TNF + MTX 47%; and 7. SpA on NSAIDs/analgesics 59%. RA patients on rituximab had significantly lower (P < 0.001) and SpA on anti-TNF monotherapy significantly better response rates compared to other treatment groups (P 0.001 to 0.033). Higher age (P < 0.001) predicted impaired immune response. Antibody titers 3 to 6 months after vaccination was generally lower compared to those within the first 3 months but no further decrease in titers were observed 6 to 22 months after vaccination.

Conclusions: Rituximab treatment severely reduced antibody response to pH1N1 influenza vaccine. The other treatment groups showed acceptable antibody responses. Protective antibody titers could be detected up to 22 months after vaccination in the current patient population, with the exception of rituximab treated patients.

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Figures

Figure 1
Figure 1
Flowchart of the study population.
Figure 2
Figure 2
Box plots with postvaccination antibody titers in relation to the time between vaccination and drawing of blood samples.
Figure 3
Figure 3
Proportion (%) of patients with positive immune response, that is seroconversion (defined as prevaccination titers <10 and postvaccination HI titers ≥40 or a ≥4-fold increase in HI titers), in different treatment groups stratified according to the number of doses of vaccine. HI, hemagglutination inhibition.
Figure 4
Figure 4
The percentage of patients with a positive immune response, that is seroconversion, (defined as prevaccination titers <10 and postvaccination HI titers ≥40 or a ≥4-fold increase in HI titers) following vaccination against H1N1 influenza stratified according to age (18 to 60 years and ≥ 60 years). The dashed lines denote seroconversion levels in healthy individuals when sufficient protection against infection is assumed (EU Committee of Human Medicinal Production criteria; CHMP). HI, hemagglutination inhibition.
See this image and copyright information in PMC

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