Effect of abatacept on the immunogenicity of 23-valent pneumococcal polysaccharide vaccination (PPSV23) in rheumatoid arthritis patients

Abstract

Introduction: Patients with rheumatoid arthritis (RA) treated with abatacept (ABT) are at increased risk for vaccine-preventable infections. The aim of the present study is to evaluate the humoral response to 23-valent pneumococcal polysaccharide (PPSV23) vaccination in RA patients receiving ABT.

Methods: The immunogenicity study was nested within a randomized, double-blind placebo-controlled study, designed to evaluate the efficacy of the PPSV23. PPSV23 was given to 111 RA patients, who were classified into three groups: RA control (n = 35), methotrexate (MTX) alone (n = 55), and ABT (n = 21). Before and 4-6 weeks after vaccination, we measured the patients' concentrations of antibodies against pneumococcal serotypes 6B and 23F using an enzyme-linked immunosorbent assay and determined their antibody functionality using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI).

Results: The pneumococcal serotype-specific IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the ABT group, the IgG responses for the 6B serotype were lower compared with those in the MTX alone or control groups, whereas the OI responses were similar to those in the other two groups. In a subgroup analysis, the pneumococcal serotype-specific IgG responses were significantly lower in both serotypes (6B and 23F) in the ABT/MTX group; however, the OI responses in the ABT group were not different from the control group. There was no association between the pneumococcal serotype-specific IgG and OI responses for the 6B serotype in patients receiving ABT in contrast to the control or MTX alone patients. No severe adverse effects were observed in any of the treatment groups.

Conclusions: OI responses indicate antibody functionality rather than simply their amount, so the similarity of these measurements between all three groups suggests that RA patients receiving ABT still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. The results suggest an influence of ABT on the humoral response to PPSV23 vaccination under MTX treatment; however, preserved opsonin responses are expected in RA patients treated with ABT plus MTX.

Trial registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012.

Fig. 1

Flow diagram of patient recruitment

Fig. 2

a Comparison of post-vaccination GMC responses in patients receiving DMARDs (control), MTX and ABT. Percentages of patients with an increase in 6B or 23F serotype-specific IgG concentration greater than two-fold are shown. There was a significant difference in the 6B serotype-specific IgG response rates between control and ABT groups (p = 0.034). Data were compared using the Pearson chi-square test. b Comparison of post-vaccination OIs responses in patients receiving DMARDs (control), MTX and ABT. Percentage of patients with an increase in OIs for serotypes 6B or 23F greater than ten-fold are shown. There was no significant difference in the response rates among control, MTX and ABT groups. GMC geometric mean concentration, DMARDS disease modifying anti-rheumatic drugs, MTX methotrexate, ABT abatacept, OIs opsonization index

Fig. 3

a Comparison of post-vaccination GMC responses in patients receiving DMARDs (control), MTX and ABT/MTX. Percentages of patients with an increase in 6B and 23F serotype-specific IgG concentration greater than two-fold are shown. There were significant differences in the 6B and 6B/23F serotype-specific IgG response rates between control and ABT/MTX groups (6B; p = 0.012, 6B + 23F; p = 0.021). Data were compared using the Pearson chi-square test. b Comparison of post-vaccination OI responses in patients receiving DMARDs (control), MTX and ABT/MTX. Percentage of patients with an increase in OIs for serotypes 6B and 23F greater than ten-fold are shown. There was no significant difference in the response rates among control, MTX and ABT/MTX groups. Data were compared using the Pearson chi-square test. GMC geometric mean concentration, DMARDS disease modifying anti-rheumatic drugs, MTX methotrexate, ABT abatacept, OIs opsonization index

Fig. 4

a Relationship between IgG and OI responses after PPSV23 vaccination. The 6B serotype-specific IgG (X axis) and OIs (Y axis) responses were plotted in the comparison of three groups (control, MTX, ABT). Positive OI responses were demonstrated in patients receiving ABT with negative IgG responses. b Comparisons of means of OIs between patients with negative or positive serotype 6B-specific IgG responses among three treatment groups (control, MTX, ABT). Error bars represent SD of mean OIs. There was no significant difference in mean OIs between patients with or without positive serotype-6B-specific IgG response in ABT group. IgG immunoglobulin G, OIs opsonization indices, MTX methotrexate, ABT abatacept, SD standard deviation