Opsonic and Antibody Responses to Pneumococcal Polysaccharide in Rheumatoid Arthritis Patients Receiving Golimumab Plus Methotrexate

Abstract

Vaccination against Streptococcus pneumoniae is recommended for rheumatoid arthritis (RA) patients receiving immunosuppressive treatments. The objective of this study was to evaluate the humoral response to 23-valent pneumococcal polysaccharide vaccination (PPSV23) in RA patients receiving methotrexate (MTX) alone or in combination with a tumor necrosis factor inhibitor, golimumab (GOM).PPSV23 was given to 114 RA patients, who were classified into three groups: RA control (n = 35), MTX alone (n = 55), and GOM + MTX (n = 24). Before and 4 to 6 weeks after vaccination, concentrations of antibodies against pneumococcal serotypes 6B and 23F were measured using an enzyme-linked immunosorbent assay and antibody functionality was determined using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI).The IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the GOM + MTX group, the IgG responses were lower than those in the MTX alone or control groups, whereas the OI responses were similar to those in the other 2 groups. Furthermore, discrepancies between the IgG and OI responses were found in GOM + MTX group. No severe adverse effect was observed in any treatment groups.OI responses indicate that antibody functionality rather than antibody quantity is important. The similarity of these measurements between all 3 groups suggests that RA patients receiving MTX + GOM still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. These results can help clinicians to better schedule and evaluate pneumococcal vaccination for RA patients.

Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: a systematic literature review for the 2019 update of EULAR recommendations

“…In this cohort, a direct correlation was shown between the postvaccination levels of antipneumococcal antibodies and the risk of pneumococcal infections: more robust antibody responses after vaccination with PCV7 were associated with lower risk of serious pneumococcal infections 123. The humoral immunogenicity and safety of PPSV23 were demonstrated in RA,76 81 109 112 113 119 124 SLE,116 125 134 and, to a limited extent, in SpA and other rheumatic diseases 115. The long-term immunogenicity of PPSV23 was evaluated in two studies in patients with RA, treated with MTX121 and biologics 130.…”

“…From the previous recommendations and up to August 2018, 34 studies53 76 81 83 84 105–133 and two meta-analyses45 77 have been published on the efficacy, immunogenicity and safety of PPSV23 and the conjugated vaccines PCV7 and PCV13, including evaluation of a combined strategy (tables 7 and 8). 106 128 133…”

“…Humoral immunogenicity of PPSV23 has been shown to be reduced by MTX,119 abatacept,109 golimumab,124 tofacitinib84 and rituximab,90 but not to be affected by certolizumab76 and belimumab 125. Immunogenicity following PCV7 vaccination is reduced by the use of MTX,110 abatacept and rituximab,108 but not by TNFα blockers 110.…”

2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases

“…On the other hand, a retrospective study on the long-term effect of PPSV23 in RA patients treated with MTX showed a relative risk of 9.7 to develop pneumonia in non-vaccinated patients 124. The humoral immunogenicity and safety of the PPSV23 has been demonstrated in RA,64 87 125–129 SLE,130–132 and to a limited extent in SpA and others 133. The long-term immunogenicity of PPSV23 has been evaluated in two studies, in RA patients treated with MTX124 and biologics, respectively 134.…”

Vaccination in rheumatology (the 2019 update of EULAR recommendations)

“…При этом Т-независимый гуморальный ответ (в том числе на ППВ-23) блокируется в значительно меньшей степени [49]. Отсутствие значимого ингибирующего влияния иФНОα на иммуногенность ППВ-23 у больных РА подтверждено другими авторами [50], в том числе в нашей работе [51]. Французские исследователи [52] показали, что последовательное применение ПКВ-13 и ППВ-23 безопасно у больных СКВ, но не дает преимуществ в иммуногенности по сравнению с таковой при назначении ППВ-23 в отдельности.…”