P-146 Assessment of Immune Responses to Pneumococcal and Influenza Vaccines in Patients Receiving Certolizumab Pegol: ERRATUM

The objective of this analysis was to determine the extent of antibody response to influenza and pneumococcal vaccination in adult patients with rheumatoid arthritis (RA) receiving certolizumab pegol (CZP) or placebo (PBO) and consider the application of these data to adult patients with Crohn’s disease (CD). Patients in this 6-week, single-blind, PBO-controlled, phase IV trial (NCT00993668) were randomized 1:1 and stratified by concomitant methotrexate to receive CZP 400 mg or PBO at Weeks 0, 2, and 4. All patients received commercially available 23-valent pneumococcal and 2009-10 trivalent subvirion influenza virus vaccines at Week 2, prior to dosing with CZP. The co-primary endpoints (assessed independently) were the percentage of patients in the per protocol set (PPS, included only those patients without protective titers at baseline) with a satisfactory humoral response, defined as a ≥2-fold titer increase in ≥3 of 6 pneumococcal antigens (6B, 9V, 14, 18C, 19F, and 23F), and a ≥4-fold increase for each of 3 influenza antigens (H1N1 [nonpandemic], H3N2, and B) at Week 6. Differences in proportions between groups were presented with a 95% confidence interval (CI). Of 224 randomized patients (CZP=110, PBO=114), 217 (96.0%) completed the study. Baseline demographics were similar between groups; 65.5% (72/110) of CZP and 68.4% (78/114) of PBO patients had concomitant methotrexate (mean dose, 16.6 mg/week). In the PPS, following pneumococcal vaccination 53.3% of CZP patients (48/90) and 62.2% (56/90) of PBO patients achieved humoral response at Week 6 (-8.9; 95%CI: -23.3, 5.5); following influenza vaccination, 54.0% (47/87) of CZP patients and 61.9% (52/84) of PBO patients achieved humoral response (-7.9; 95% CI: -22.7; 6.9). There was a >2-fold increase from baseline to Week 6 in titers in both treatment groups for each of the antigens tested in all patients including those with protective titers at baseline (full analysis set, FAS). Following vaccination, 62.6% (67/107) of CZP and 65.5% (72/110) of PBO patients and 71.0% (76/107) of CZP and 77.1% (84/109) of PBO patients in the FAS developed protective pneumococcal and influenza antibody titers, respectively. Responses to pneumococcal and influenza antigens were reduced in both groups who received concomitant methotrexate vs those who did not (CZP vs PBO: pneumococcal antigens, with methotrexate = 45.2% [28/62] vs 49.2% [30/61], without methotrexate = 71.4% [20/28] vs 89.7% [26/29]; influenza antigens, with concomitant methotrexate = 47.4% [27/57] vs 50.9% [29/57], without concomitant methotrexate = 66.7% [20/30] vs 85.2% [23/27]). Incidence of adverse events was comparable across groups; most events were mild to moderate in intensity. There was 1 death in the CZP group (unrelated to study drug) and none in the PBO group. Humoral responses to pneumococcal and influenza vaccines were comparable in patients receiving treatment with CZP and PBO. Vaccine responses were reduced in both treatment groups with concomitant methotrexate. These results indicate that patients receiving CZP can be effectively immunized with pneumococcal and influenza vaccines. Although these data were not collected in CD patients, they should be considered when CD patients require immunization with pneumococcal and influenza vaccines.