Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Efficacy and Safety of Certolizumab Pegol Plus Methotrexate in Japanese Rheumatoid Arthritis Patients with An Inadequate Response to Methotrexate.

Yamamoto¹, Kazuhiko, Takeuchi², Tsutomu, Yamanaka³, Hisashi, Ishiguro⁴, Naoki, Tanaka⁵, Yoshiya, Eguchi⁶, Katsumi, Watanabe⁷, Akira

Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
UCB Inc, Chiyoda, Tokyo, Japan
Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
Sapporo Medical Center NTT EC, Sapporo, Japan
Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
Institute of Rheumatology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
Nagoya University, Graduate School & Faculty of Medicine, Nagoya, Aichi, Japan
University of Occupational & Environmental Health, Kitakyushu, Fukuoka, Japan
Sasebo City General Hospital, Sasebo, Nagasaki, Japan
Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
University of Toyama School of Medicine, Toyama, Toyama, Japan
Otsuka Pharmaceutical Co., Ltd, Shinagawa-ku, Tokyo, Japan

Background/Purpose:

Certolizumab pegol (CZP) as add-on therapy to methotrexate (MTX) provided rapid and sustained efficacy in RA patients (pts) in multiple international clinical trials.^1,2 The objective of this study was to investigate the efficacy and safety of CZP + MTX in Japanese pts with active RA and an inadequate response to MTX.

Methods:

In this 24-week (wk), Phase II/III, multicenter, double-blind, randomized, placebo-controlled, study (NCT00791999), Japanese pts with active RA and an inadequate response to MTX were randomized (1:1:1:1) to 1 of 4 treatment groups: CZP 100, 200, or 400 mg or placebo (PBO) + MTX every 2 wks (Q2W). Per study design, pts in the CZP groups received induction dosing with 200 mg (100 mg group) or 400 mg (200 and 400 mg groups) at Wks 0, 2, and 4. Pts who did not achieve an ACR20 response at Wks 12 and 14 were withdrawn from the study at Wk 16 and were eligible to enter an open-label extension study, as were pts completing the study. Primary efficacy end point was ACR20 response at Wk 12.

Results:

A total of 316 pts were randomized. Demographic and baseline (BL) characteristics were similar between treatment groups: RA disease duration ranged from 5.6 to 6.0 years, DAS28(ESR) from 6.19 to 6.46, HAQ-DI from 1.12 to 1.19, and MTX dose from 7.4 to 7.6 mg/wk across groups. The primary end point was met; ACR20 and ACR50 response rates were significantly higher in each CZP group compared with PBO at Wks 12 and 24 (Table). Differences in CZP ACR20 response rates vs PBO were significant 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-treated groups vs PBO; differences seen with the 100 mg Q2W dose were not significant vs PBO. Improvements in all ACR core set of disease activity measures, including physical function, were observed as early as Wk 1 and were sustained to Wk 24 at all CZP doses. CZP was well tolerated and no new safety signals were identified. SAEs ranged from 4.2% to 5.9% in the CZP groups (with 4 pts developing serious infections or infestations) vs 1.3% in the PBO group. There were no cases of TB or deaths.

Table. Efficacy of CZP + MTX at Wks 12 and 24 in Japanese RA pts

	CZP 100 mg n=72	CZP 200 mg n=82	CZP 400 mg n=85	PBO n=77
Wk 12
ACR20,% responders^a	62.5*	76.8*	77.6*	28.6
ACR50,% responders^a	34.7*	41.5*	51.8*	7.8
ACR70,% responders^a	13.9	20.7	25.9	0.0^c
DAS28(ESR), LS mean change from BL (SE)^b	-1.89 (0.14)*	-2.23 (0.13)*	-2.33 (0.13)*	-0.56 (0.13)
HAQ-DI, LS mean change from BL (SE)^b	-0.42 (0.05)*	-0.47 (0.05)*	-0.51 (0.05)*	-0.16 (0.05)
Pain VAS, LS mean change from BL (0–100 mm) (SE)^b	-23.8 (2.5)*	-25.6 (2.3)*	-28.7 (2.3)*	-8.9 (2.4)
DAS28(ESR) remission rate^b,%	8.3	16.0	11.8	0.0^c
Moderate or good EULAR response^b,%	76.4	86.4	90.6	36.4^c
Wk 24
ACR20,% responders^a	61.1*	73.2*	71.8*	24.7
ACR50,% responders^a	44.4*	54.9*	54.1*	16.9
ACR70,% responders^a	26.4*	29.3*	30.6*	1.3
DAS28(ESR), LS mean change from BL (SE)^b	-2.11 (0.16)*	-2.46 (0.15)*	-2.69 (0.14)*	-0.63 (0.15)
HAQ-DI, LS mean change from BL (SE)^b	-0.43 (0.06)**	-0.55 (0.05)**	-0.57 (0.05)**	-0.18 (0.06)
Pain VAS, LS mean change from DL (0–100 mm) (SE)^b	-26.9 (2.6)*	-27.9 (2.5)*	-31.9 (2.4)*	-10.6 (2.6)
DAS28(ESR) remission rate^b,%	20.8	17.1	25.9	0.0^c
Moderate or good EULAR response^b,%	77.8	85.4	89.4	29.9^c
mTSS, LS mean change from BL (SE)^d,e	1.04 (0.41)^g	0.21 (0.38)**	0.65 (0.37)**	2.78 (0.39)
mTSS,% non-progressors^d,e,f	62.9^g	74.1**	70.2**	47.4
^a NRI.^bLOCF.^cp Value not calculated.^dThe actual number of subjects in the summaries varies slightly from n=316 due to nonimputable missing data for each parameter.^eLin ext.^fmTSS non-progressor: mTSS change from BL score at WK 24 <0.5.^gNot significant compared with PBO. LS = least square.
p<0.001,*p<0.01 each CZP group vs PBO. ACR response, DAS28(ESR) remission rate, mTSS non-progressors and EULAR response was assessed by logistic regression. DAS28(ESR), HAQ-DI, pain VAS and mTSS LS mean change from BL were assessed by analysis of covariance (ANCOVA).

Conclusion:

Treatment with CZP + MTX resulted in a rapid and sustained reduction in RA signs and symptoms, inhibited progression of structural joint damage, and improved physical function in Japanese RA pts with an inadequate response to MTX. The 200 mg Q2W maintenance dose showed numerically greater clinical efficacy and better inhibition of radiographic progression compared with the 100 mg Q2W dose. No additional benefit was observed with the 400 mg Q2W dose vs the 200 mg Q2W dose. These results confirm the findings of the RAPID studies^{1, 2} and substantiate 200 mg Q2W as the optimal maintenance dosing for CZP.

References

1.Keystone, E, et al. Arthritis Rheum 2008;58:3319–3329.

2.Smolen, J, et al. Ann Rheum Dis 2009;68:797–804.

To cite this abstract, please use the following information:
Yamamoto, Kazuhiko, Takeuchi, Tsutomu, Yamanaka, Hisashi, Ishiguro, Naoki, Tanaka, Yoshiya, Eguchi, Katsumi, et al; Efficacy and Safety of Certolizumab Pegol Plus Methotrexate in Japanese Rheumatoid Arthritis Patients with An Inadequate Response to Methotrexate. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1218
DOI:

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