Clinical Response At 12 Weeks Predicts Long-Term Remission and the Extent of Radiographic Progression in Japanese Patients with Rheumatoid Arthritis Treated with Certolizumab Pegol with and without Methotrexate Coadministration

Tsutomu Takeuchi¹, Kazuhiko Yamamoto², Hisashi Yamanaka³, Naoki Ishiguro⁴, Yoshiya Tanaka⁵, Katsumi Eguchi⁶, Akira Watanabe⁷, Hideki Origasa⁸, Toshiharu Shoji⁹, Nobuyuki Miyasaka¹⁰ and Takao Koike¹¹, ¹Keio University School of Medicine, Tokyo, Japan, ²Department of Allergy & Rheumatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan, ³Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, ⁴Department of Orthopedic Surgery, Nagoya University, Graduate School & Faculty of Medicine, Nagoya, Aichi, Japan, ⁵The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, ⁶Sasebo City General Hospital, Sasebo, Nagasaki, Japan, ⁷Research Division for Development of Anti-Infectious Agents, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan, ⁸Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine, Toyama, Toyama, Japan, ⁹Department of Clinical Research and Development, Otsuka Pharmaceutical Co., Ltd, Shinagawa-ku, Tokyo, Japan, ¹⁰Department of Medicine and Rheumatology and Global Center of Excellence Program, Tokyo Medical and Dental University, Tokyo, Japan, ¹¹Sapporo medical center NTT EC, Sapporo, Japan

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: certolizumab pegol and rheumatoid arthritis, Japanese, treatment

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy

Session Type: Abstract Submissions (ACR)

Background/Purpose: The majority of patients (pts) with active rheumatoid arthritis (RA) have previously been shown to respond during the first 12 weeks (wks) of certolizumab pegol (CZP) treatment; additionally, a lack of DAS28 improvement by Wk12 predicts failure to achieve low disease activity (LDA) at later timepoints.¹This post hoc analysis investigated whether the magnitude of DAS28(ESR) nonresponse to CZP at Wk12 of therapy can predict the likelihood of achieving remission (DAS28(ESR)<2.6) and extent of radiographic progression after 1 year (yr) (52-56 wks) of CZP treatment in Japanese pts receiving coadministered MTX (JRAPID, NCT00851318), DMARDs other than MTX or CZP monotherapy (HIKARI, NCT00850343).

Methods: Both studies included a 24 Wk double blind phase (CZP 400mg Wks 0, 2, 4, then CZP 200mg every other week (Q2W)), followed by open-label treatment for 28 Wks with CZP 200mg Q2W or CZP 400mg every 4 wks (Q4W). The mean change in mTSS and the proportion of pts who achieved remission at 1 yr was assessed according to the level of DAS28 response (ie, DAS28(ESR) change from baseline [CFB] ≥0.6 and ≥1.2 units) at Wk12. Last observation carried forward (LOCF) imputation was used for pts who withdrew.

Results: 82 J-RAPID and 116 HIKARI CZP treated pts were included. J-RAPID and HIKARI pts had a mean baseline DAS28(ESR) of 6.19 and 6.09, and mean mTSS total of 50.4 and 36.5, respectively. Overall, 77% of J-RAPID pts and 74% of HIKARI pts had a ≥1.2 DAS28(ESR) response at Wk12. Remission was achieved by 32.9% and 27.6% of the original J-RAPID and HIKARI CZP ITT populations at 1 yr. Pts who did not achieve a DAS28(ESR) change of ≥1.2 at Wk12, had a <7% chance of achieving remission at Wk52 (Table) and had greater radiographic progression at 1 yr than responders. Failure to achieve remission at 1 yr and the extent of radiographic progression was also dependent on the magnitude of DAS28(ESR) change at Wk12. Pts with a DAS28(ESR) response of <0.6 had a lower rate of remission and greater radiographic progression at 1 yr compared to pts with a DAS28(ESR) response of <1.2 (Table). Similar results were observed in both the J-RAPID and HIKARI populations.

Conclusion: The majority of Japanese pts responded to treatment with CZP at Wk12 in the broad pt population represented by these studies. Likelihood of remission and extent of radiographic progression after 1 year could be predicted at Wk12 based on the magnitude of change in DAS28(ESR) in pts.

References 1. van der Heijde D. Ann Rheum Dis 2010;69(suppl 3):505

Table: Wk 12 response predicts remission rate and mean mTSS total score change after 1 year