title: Antibody response to pneumococcal and influenza vaccination in patients with rheumatoid arthritis receiving abatacept.
abstract: Patients with rheumatoid arthritis (RA), including those treated with biologics, are at increased risk of some vaccine-preventable infections. We evaluated the antibody response to standard 23-valent pneumococcal polysaccharide vaccine (PPSV23) and the 2011-2012 trivalent seasonal influenza vaccine in adults with RA receiving subcutaneous (SC) abatacept and background disease-modifying anti-rheumatic drugs (DMARDs).
  
  
  
  Two multicenter, open-label sub-studies enrolled patients from the ACQUIRE (pneumococcal and influenza) and ATTUNE (pneumococcal) studies at any point during their SC abatacept treatment cycle following completion of ≥3 months' SC abatacept. All patients received fixed-dose abatacept 125 mg/week with background DMARDs. A pre-vaccination blood sample was taken, and after 28 ± 3 days a final post-vaccination sample was collected. The primary endpoint was the proportion of patients achieving an immunologic response to the vaccine at Day 28 among patients without a protective antibody level to the vaccine antigens at baseline (pneumococcal: defined as ≥2-fold increase in post-vaccination titers to ≥3 of 5 antigens and protective antibody level of ≥1.6 μg/mL to ≥3 of 5 antigens; influenza: defined as ≥4-fold increase in post-vaccination titers to ≥2 of 3 antigens and protective antibody level of ≥1:40 to ≥2 of 3 antigens). Safety and tolerability were evaluated throughout the sub-studies.
  
  
  
  Pre- and post-vaccination titers were available for 113/125 and 186/191 enrolled patients receiving the PPSV23 and influenza vaccine, respectively. Among vaccinated patients, 47/113 pneumococcal and 121/186 influenza patients were without protective antibody levels at baseline. Among patients with available data, 73.9 % (34/46) and 61.3 % (73/119) met the primary endpoint and achieved an immunologic response to PPSV23 or influenza vaccine, respectively. In patients with pre- and post-vaccination data available, 83.9 % in the pneumococcal study demonstrated protective antibody levels with PPSV23 (titer ≥1.6 μg/mL to ≥3 of 5 antigens), and 81.2 % in the influenza study achieved protective antibody levels (titer ≥1:40 to ≥2 of 3 antigens) at Day 28 post-vaccination. Vaccines were well tolerated with SC abatacept with background DMARDs.
  
  
  
  In these sub-studies, patients with RA receiving SC abatacept and background DMARDs were able to mount an appropriate immune response to pneumococcal and influenza vaccines.
  
  
  
  NCT00559585 (registered 15 November 2007) and NCT00663702 (registered 18 April 2008).
authors.affiliation: Schlosspark-Klinik University Medicine, Berlin, Germany. rieke.alten@schlosspark-klinik.de.|University Medicine Berlin, Berlin, 14059, Germany. rieke.alten@schlosspark-klinik.de.
authors.forename: Rieke
authors.initials: R
authors.lastname: Alten
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Clifton O
authors.initials: CO
authors.lastname: Bingham
authors.affiliation: Metroplex Clinical Research Center, Dallas, TX, USA.
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Cohen
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Wong
authors.affiliation: Stanford University, Palo Alto, CA, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
mesh_terms: D000069594:Abatacept / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000009:adverse effects / Q000276:immunology*; D014611:Vaccination
chemical_list: C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D007252:Influenza Vaccines; D022242:Pneumococcal Vaccines; D000069594:Abatacept
keywords: Abatacept; Immunization; Influenza; Pneumococcal; Rheumatoid arthritis; Vaccination