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Please use this identifier to cite or link to this item: http://hdl.handle.net/10805/1977

Title: Influenza Vaccination in Patients with Rheumatoid Arthritis under treatment with TNFα Blockers or co-stimulus Inhibitor
Authors: MILANETTI, FRANCESCA
Tutor: D'AMELIO, RAFFAELE
NISINI, ROBERTO
Keywords: RHEUMATOID ARTHRITIS
INFLUENZA VACCINATION
Issue Date: 27-Feb-2013
Abstract: Influenza vaccination in patients with rheumatoid arthritis under treatment with TNFα blockers or co-stimulus inhibitors Objective To evaluate the safety and the immunogenicity of the trivalent seasonal non-adjuvanted anti-influenza vaccine in rheumatoid arthritis RA patients receiving distinct classes of anti tumor necrosis factor -TNF agents or inhibitors of co-stimulus compared with patients with RA or SLE receiving DMARDs and healthy controls and the effect of a simultaneous 23valent anti-pneumococcal or pandemic monovalent MF59-H1N1adjuvanted vaccine. Methods 85 patients with RA, under treatment with TNFα blockers or inhibitors of co-stimulus, all with stable disease (under the same treatment during the last six months), were immunized at least once with nonadjuvanted trivalent influenza vaccine during three consecutive influenza seasons and compared with 42 HC. In the second season 30 RA patients (13 HC) received simultaneously also adjuvanted pandemic H1N1 vaccination. In the first and third season, instead, respectively 19 and 15 RA (10 and 6 HC) patients received simultaneously also polysaccaride pneumococcal vaccination. In the last season 9 RA and 16 SLE under treatment with DMARDS were also enrolled. Sera were analyzed by hemagglutination-inhibition (HAI) test, according to standard procedures, and vaccine immunogenicity was evaluated according to the Committee for Human Medicinal Products (CHMP) guidelines. Seroprotection, seroconversion (SC), geometric mean titre (GMT), GMT increase, T-reg cells, anti-nuclear antibodies (ANA), adverse events and disease acrivity (according to clinimetric indices) were evaluated at baseline and at 30 and 180 days after vaccination/s. In the second season a study on T cell memory subset modification and aspecific cellular immune response was performed in a patient soubgroup. Moreover the effect of the polisaccaride vaccine on cellular immune response has been analyzed on stimulated PBMC in vitro through cytofluorimetry and ELISA. Results Safety No severe adverse events, ANA appearance/increase or disease reactivation were observed during the 3 influenza seasons. Antibodies 2008/2009: RA patients did not fulfill any immunogenity criteria for A/Brisbane/59/07 (H1), 1 for B/Florida/4/06 , and 3 for A/Brisbane/10/07 (H3). HC, instead, met all the 3 criteria for A/Brisbane/59/07 (H1) and A/Brisbane/10/07 (H3) and only one for B/Florida/4/06. However, the mean increase in geometric mean titer was not statistically different between RA and HC for any antigen. 2009/2010: Both HC and RA patients fulfilled all the 3 immunogenity criteria for the seasonal (A/Brisbane/59/07 (H1) A/Brisbane/10/07 (H3) B/Brisbane/60/08) and the pandemic (A/California/7/2009 (H1)) antigens with no statistical difference between groups. 2010/2011: RA and SLE patients under treatment with DMARDS and HC fullfilled all the 3 immunogenity criteria, while RA under treatment with biological agents only 1 for A/Perth/16/09 (H3) and 2 for A/California/7/2009 (H1) and B/Brisbane/60/08. Increase in GMT versus H1(p 0.008) and H3 (p 0.046) was statistically different between RA on biological and HC and versus H1 (p 0.034) and B (p 0.003) between RA on biological and RA on DMARDS in subjects immunized only with influenza. Among HC and RA patients under treatment with DMARDS immunized also with pneumococcal vaccine no response was observed vs H3 compared to the complete response in subjects immunized with only influenza (HC p 0.034) No significant difference in vaccine response has been observed among the different groups of biological agents (Etanercept, Infliximab, adalimumab, abatacept) The cohort follow-up revealed increase in GMT and seroprotection rate for A but not for B antigens. Cell-mediated immunity An increase in Tregs, activated cytokine-producing cells, T naïve and CM subsets and a decrease in T EM and TD lymphocytes, 30 days after vaccination, was observed both in patients and controls. In vitro studies showed that the presence of the polysaccharide vaccine inhibits specific and aspecific cellular immune response in a dose-dependent manner. Conclusion Response to seasonal influenza vaccination in RA and SLE patients under treatment with DMARDS is comparable to HC. The suboptimal response in the first and third seasons both in RA patients under treatment with biological agents and HC could be partially due to the simultaneous pneumococcal vaccination. Adjuvanted influenza vaccine looks to be safe and able to achieve strong immunogenicity, comparable to HC, even in this group of patients. The increase at T1 in activated T cells reflects the predominant implication of Th1 response to vaccination.
URI: http://hdl.handle.net/10805/1977
Research interests: VACCINATIONS AND HSCT IN AUTOIMMUNE DISEASES
Appears in PhD:SCIENZE PASTEURIANE

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