Background/Purpose: The extent of antibody response to influenza and pneumococcal vaccination was evaluated in adult patients (pts) with rheumatoid arthritis (RA) receiving certolizumab pegol (CZP) or placebo (PBO).
Method: This was a 6-week (wk) randomized, single-blind, PBO-controlled, phase IV trial followed by a 6-month open-label phase (NCT00993668). In the 6-wk phase, pts were randomized 1:1 and stratified by concomitant (MTX) use to receive CZP 400 mg or PBO at Wks 0, 2, and 4. All pts received commercially available 23‑valent pneumococcal and 2009-10 trivalent subvirion influenza virus vaccines at Wk 2, prior to dosing with CZP. The co-primary endpoints (assessed independently) were the percentage of pts, in the per protocol set (PPS, included only those pts without protective titers at baseline [BL]) 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 Wk 6 (4 wks post-vaccination). Differences in proportions between groups were presented with a 95% confidence interval (CI). The results from 6-wk phase are reported.
Result: Of 224 randomized pts (CZP = 110; PBO = 114), 217 (96.9%) completed the 6-wk single-blind phase. BL demographics were similar between groups; 65.5% (72/100) of CZP and 68.4% (78/114) of PBO pts had concomitant MTX use (mean dose,16.6 mg/wk) at BL. In the PPS, following pneumococcal vaccination 53.3% of CZP pts (48/90) and 62.2% (56/90) of PBO pts achieved humoral response, at Wk 6 (8.9; 95% CI: 23.3; 5.5). Following influenza vaccination, 54.0% (47/87) of CZP pts and 61.9% (52/84) of PBO pts achieved humoral response, at Wk 6 (7.9; 95% CI: 22.7; 6.9). There was a >2-fold increase from BL to Wk 6 in titers in both treatment groups for each of the antigens tested in all pts including those with protective titers at BL (full analysis set, FAS). Following vaccination, 62.6% (67/107) of CZP and 65.5% (72/110) of PBO pts and 71.0% (76/107) of CZP and 77.1% (84/109) of PBO pts in the FAS developed protective pneumococcal and influenza antibody titers, respectively. Responses to pneumococcal and influenza antigens were reduced in both CZP and PBO pts who received concomitant MTX vs those who did not (CZP vs PBO: pneumococcal antigens, with concomitant MTX = 45.2% [28/62] vs 49.2% [30/61], without concomitant MTX = 71.4% [20/28] vs 89.7% [26/29]; influenza antigens, with concomitant MTX = 47.4% [27/57] vs 50.9% [29/57], without concomitant MTX = 66.7% [20/30] vs 85.2% [23/27]). Incidence of adverse events was comparable in CZP and PBO; most events were mild to moderate in intensity. There was 1 death in CZP group (bladder cancer diagnosed during study; unrelated to study drug) and none in the PBO group.
Conclusion: Humoral responses to pneumococcal and influenza vaccines were comparable in RA pts receiving treatment with CZP and PBO. Vaccine responses were reduced in both treatment groups with concomitant MTX therapy. These results indicate that RA pts receiving CZP can be effectively immunized with pneumococcal and influenza vaccines.
*Current affiliation: Merck Research Laboratories, Rahway, NJ, USA
Disclosure: A. J. Kivitz, UCB Inc, 5 ; J. Schechtman, UCB Inc, 5, UCB Inc, 8 ; M. Texter, UCB Inc, 3 ; A. Fichtner, UCB Inc, 3 ; E. Chartash*, UCB Inc, 1, UCB Inc, 3 .