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SAT0173 Baseline Parameters Identified in Early, Methotrexate-Naïve Rheumatoid Arthritis Patients with Better Outcomes with Certolizumab Pegol+Methotrexate Compared to Placebo+Methotrexate: Post-Hoc Analyses of C-OPERA, A Randomized, Controlled, Phase 3 Study
  1. T. Atsumi1,
  2. K. Yamamoto2,
  3. T. Takeuchi3,
  4. H. Yamanaka4,
  5. N. Ishiguro5,
  6. Y. Tanaka6,
  7. K. Eguchi7,
  8. A. Watanabe8,
  9. H. Origasa9,
  10. T. Shoji10,
  11. O. Togo10,
  12. T. Okada11,
  13. D. van der Heijde12,
  14. N. Miyasaka13,
  15. T. Koike1,14
  1. 1Hokkaido University Graduate School of Medicine, Hokkaido
  2. 2The University of Tokyo
  3. 3Keio University School of Medicine
  4. 4Tokyo Women's Medical University, Tokyo
  5. 5Nagoya University, Nagoya
  6. 6University of Occupational and Environmental Health, Kitakyushu
  7. 7Sasebo City General Hospital, Nagasaki
  8. 8Tohoku University, Sendai
  9. 9University of Toyama School of Medicine, Toyama
  10. 10UCB Pharma
  11. 11Astellas Pharma Inc., Tokyo, Japan
  12. 12Leiden University Medical Centre, Leiden, Netherlands
  13. 13Tokyo Medical and Dental University, Tokyo
  14. 14NTT Sapporo Medical Center, Sapporo, Japan

Abstract

Background The C-OPERA study (NCT01451203) demonstrated better clinical outcomes of certolizumab pegol (CZP)+MTX compared to placebo (PBO)+MTX in Japanese MTX-naïve early RA patients (pts) with poor prognostic factors.1

Objectives To identify factors associated with better outcomes of CZP+MTX compared to PBO+MTX at 1 year using subgroup analyses by baseline (BL) factors.

Methods Pts with ≤12 months persistent RA fulfilling 2010 ACR/EULAR classification criteria2 were enrolled in C-OPERA, a multicenter, double-blind, randomized study. Pts were MTX-naïve, with moderate disease activity (DAS28[ESR]≥3.2), positive ACPA (≥3xULN), and either RF positive or had bone erosion on radiographs of hands/feet. Pts were randomized 1:1 to CZP+MTX or PBO+MTX. CZP 400mg was administered at Weeks (Wks) 0, 2, and 4, followed by CZP 200mg Q2W to Wk52. Unless precluded by tolerability, MTX was started at 8mg/wk and escalated to 16mg/wk over 8 wks. We report association of BL parameters and mean MTX dose with radiographic progression (change from BL [CFB] in modified total Sharp score [mTSS]) and clinical remission (DAS28<2.6) at Wk52.

Results In PBO+MTX arm, higher BL DAS28, CRP, mTSS, HAQ-DI and serum MMP-3 were associated with greater radiographic progression at Wk52, whereas CZP+MTX still inhibited progression of structural damage in these pts despite higher risk of progression.3 No positive trend of MTX dose with inhibitory effect on CFB in mTSS was observed overall. In the PBO+MTX arm, higher BL DAS28 and CRP were associated with lower DAS28 remission rate at Wk52, suggesting BL factors associated with either radiographic progression or disease activity may differ. Lower dose MTX group (8–≤12mg/wk) showed lower DAS28 remission rate compared to high dose group (>12–16mg/wk) (30.5% vs 42.9%). DAS28 remission rate was higher in CZP+MTX compared to PBO+MTX, particularly in pts with high BL parameters.

Conclusions CZP+MTX showed better clinical outcomes compared to PBO+MTX, particularly in pts with higher risk of progression identified by BL factors. Therefore, this subgroup of MTX-naïve early RA pts may need combination treatment with CZP+MTX to inhibit progression of structural damage.

References

  1. Atsumi T. Ann Rheum Dis 2014;73(2):S484.

  2. Aletaha D. Ann Rheum Dis 2010;69:1580–1588.

  3. Atsumi T. Arthritis Rheumatol 2014;66(11):S1078.

Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma.

Disclosure of Interest T. Atsumi Speakers bureau: Astellas, Bristol-Myers, Chugai and Mitsubishi-Tanabe, K. Yamamoto Grant/research support from: UCB Pharma, Pfizer, Abbott, Santen, Mitsubishi-Tanabe and Eisai, Consultant for: UCB Pharma, Pfizer, Abbott, BMS, Roche, Chugai, Mitsubishi-Tanabe and Eisai, T. Takeuchi Grant/research support from: Abott, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe, Nippon Shinyaku, Otsuka, Pfizer, Sanofi-Aventis, Santen, Takeda and Teijin, Consultant for: AstraZeneca, Eli Lilly, Novartis, Mitsubishi-Tanabe and Asahi Kasei, Speakers bureau: UCB Pharma, Abbott, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer and Takeda, H. Yamanaka Grant/research support from: UCB Pharma, Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer and Takeda, Consultant for: UCB Pharma, Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer and Takeda, N. Ishiguro Grant/research support from: Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken and Pfizer, Speakers bureau: Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken, Pfizer, Taisho-Toyama and Otsuka, Y. Tanaka Grant/research support from: BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, Abbvie, Daiichi-Sankyo, Consultant for: UCB Pharma, Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, Asahi Kasei, Speakers bureau: UCB Pharma, Mitsubishi-Tanabe, Abbott, Abbvie, Eisai, Chugai, Janssen, Pfizer, Takeda, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Eli Lilly, Quintiles, MSD, Asahi Kasei, K. Eguchi Consultant for: UCB Pharma, A. Watanabe Grant/research support from: Daiichi-Sankyo, Kyorin, Shionogi, Taisho, Dainippon-Sumitomo, Taiho, Toyama Chemical and Meiji Seika, Speakers bureau: SD, GSK, Shionogi, Daiichi-Sankyo, Taisho-Toyama, Dainippon-Sumitomo, Mitsubishi-Tanabe, Pfizer, H. Origasa Consultant for: UCB Pharma and Astellas, T. Shoji Employee of: UCB Pharma, O. Togo Employee of: UCB Pharma, T. Okada Employee of: Astellas, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Vertex, Employee of: Imaging Rheumatology bv., N. Miyasaka Grant/research support from: Pfizer, Takeda, Mitsubishi-Tanabe, Chugai, Abbott, Eisai and Astellas, T. Koike Consultant for: Abbvie, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Pfizer, Santen, Taisho-Toyama, Takeda, Teijin, UCB Pharma, Speakers bureau: UCB Pharma, Pfizer, Chugai, Abbott, Mitsubishi-Tanabe, Takeda, Eisai, Santen, Astellas, Taisho-Toyama, BMS, Teijin and Daiichi-Sankyo

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