Background/Purpose: Certolizumab pegol (CZP) as monotherapy or as add-on to methotrexate (MTX) provided rapid and sustained efficacy in RA patients (pts) in international clinical trials.1–3 The objective of this study was to investigate efficacy and safety of CZP in Japanese pts with active RA in whom MTX could not be administered.
Method: In this 24-week (wk), Phase III, double-blind, randomized, placebo-controlled study (NCT00791921), pts were randomized to CZP 200 mg (following induction dosing of 400 mg at Wks 0, 2, and 4) or placebo (PBO) every 2 wks. Pts not achieving ACR20 at Wks 12 and 14 withdrew at Wk 16 and were eligible to enter an open-label extension, as were pts completing the study. Primary efficacy endpoint was ACR20 at Wk 12. ACR20 response rates and radiographic progression were also investigated in subgroups of pts receiving CZP monotherapy or concomitant DMARDs.
Result: Demographic and baseline (BL) characteristics of the 230 randomized pts were similar between CZP and PBO groups: mean RA disease duration 5.4 and 5.8 y, mean HAQ-DI 1.05 and 1.21, mean DAS28(ESR) 6.09 and 6.30, respectively. At BL, 53.4% of CZP pts (vs 57% PBO pts) received concomitant DMARDs and 46.6% received CZP monotherapy. The primary endpoint was met; ACR20 and ACR50 responses were significantly higher in all CZP groups vs PBO at Wks 12 and 24 (Table). Significant differences in ACR20 responses were seen as early as Wk 1 and sustained to Wk 24. At Wk 24, mean radiographic progression from BL was reduced and more pts were mTSS non-progressors in the CZP group (Table). At Wk 12, ACR20 responses were higher in CZP pts either on monotherapy or with concomitant DMARDs, with similar treatment differences of 51.1 points and 54.2 points, respectively (CZP vs PBO: monotherapy, 59.3% vs 8.2%; concomitant DMARDs, 74.2% vs 20.0%). Preliminary post-hoc analyses showed that at Wk 24, CZP significantly inhibited radiographic progression when administered as monotherapy (mTSS mean change from BL: 3.65 PBO vs 0.68 CZP, p=0.0087) or with concomitant DMARDs (mTSS mean change from BL: 1.61 PBO and CZP 0.24, p=0.001). CZP was well tolerated with no new safety signals. 11.2% of CZP pts experienced SAEs vs 2.6% in PBO (with 4 and 1 pts developing serious infections or infestations, respectively). There was 1 death in the CZP group and no cases of TB.
Conclusion: Treatment with CZP in Japanese RA pts in whom MTX could not be administered resulted in rapid and sustained improvement of RA signs and symptoms, inhibited progression of structural joint damage, and ameliorated physical function. Efficacy and radiographic results were consistent regardless of use of concomitant DMARDs; notably, CZP showed significant inhibition of radiographic progression when used as monotherapy.
1. Fleischmann R, et al. Ann Rheum Dis 2009;68:805–811.
2. Keystone E, et al. Arthritis Rheum 2008;58:3319–3329.
3. Smolen J, et al. Ann Rheum Dis 2009;68:797–804.
Disclosure: K. Yamamoto, Otsuka Pharmaceutical Co., Ltd, 5 ; T. Takeuchi, Otsuka Pharmaceutical Co., Ltd, 5 ; H. Yamanaka, Otsuka Pharmaceutical Co., Ltd, 5, Otsuka Pharmaceutical Co., Ltd, 2, UCB Inc, 5, UCB Inc, 2 ; N. Ishiguro, Otsuka Pharmaceutical Co., Ltd, 5 ; Y. Tanaka, Otsuka Pharmaceutical Co., Ltd, 5 ; K. Eguchi, Otsuka Pharmaceutical Co., Ltd, 5 ; A. Watanabe, Otsuka Pharmaceutical Co., Ltd, 5 ; H. Origasa, Ostsuka Pharmaceutical Co., Ltd, 5 ; K. Iwai, Otsuka Pharmaceutical Co., Ltd, 3 ; Y. Sakamaki, UCB Inc, 3 ; N. Miyasaka, Otsuka Pharmaceutical Co., Ltd, 5 ; T. Koike, Otsuka Pharmaceutical Co., Ltd, 5 .