Article Text

Download PDFPDF

Extended report
Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial
  1. Tatsuya Atsumi1,
  2. Yoshiya Tanaka2,
  3. Kazuhiko Yamamoto3,
  4. Tsutomu Takeuchi4,
  5. Hisashi Yamanaka5,
  6. Naoki Ishiguro6,
  7. Katsumi Eguchi7,
  8. Akira Watanabe8,
  9. Hideki Origasa9,
  10. Shinsuke Yasuda1,
  11. Yuji Yamanishi10,
  12. Yasuhiko Kita11,
  13. Tsukasa Matsubara12,
  14. Masahiro Iwamoto13,
  15. Toshiharu Shoji14,
  16. Osamu Togo14,
  17. Toshiyuki Okada15,
  18. Désirée van der Heijde16,
  19. Nobuyuki Miyasaka17,
  20. Takao Koike1,18
  1. 1 Hokkaido University Graduate School of Medicine, Sapporo, Japan
  2. 2 The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan
  3. 3 Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  4. 4 Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  5. 5 Tokyo Women's Medical University, Tokyo, Japan
  6. 6 Nagoya University Graduate School and Faculty of Medicine, Nagoya, Japan
  7. 7 Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital, Sasebo, Nagasaki, Japan
  8. 8 Tohoku University, Sendai, Japan
  9. 9 Division of Biostatistics and Clinical Epidemiology, The University of Toyama Graduate School of Medicine, Toyama, Japan
  10. 10 Hiroshima Rheumatology Clinic, Hiroshima, Japan
  11. 11 Yokohama Rosai Hospital, Yokohama, Japan
  12. 12 Matsubara Mayflower Hospital, Kato, Japan
  13. 13 Division of Rheumatology and Clinical Immunology, Jichi Medical University, Tochigi, Japan
  14. 14 UCB Pharma, Tokyo, Japan
  15. 15 Astellas Pharma Inc., Tokyo, Japan
  16. 16 Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
  17. 17 Department of Rheumatology, Tokyo Medical and Dental University, Tokyo, Japan
  18. 18 Sapporo Medical Center NTT EC, Sapporo, Hokkaido, Japan
  1. Correspondence to: Professor Tatsuya Atsumi, Division of Rheumatology, Endocrinology and Nephrology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan; at3tat{at}med.hokudai.ac.jp

Abstract

Objectives To investigate the clinical impact of 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year methotrexate (MTX) therapy, compared with 2-year therapy with MTX alone.

Methods MTX-naïve patients with early rheumatoid arthritis (RA) with poor prognostic factors were eligible to enter Certolizumab-Optimal Prevention of joint damage for Early RA (C-OPERA), a multicentre, randomised, controlled study, which consisted of a 52-week double-blind (DB) period and subsequent 52-week post treatment (PT) period. Patients were randomised to optimised MTX+CZP (n=159) or optimised MTX+placebo (PBO; n=157). Following the DB period, patients entered the PT period, receiving MTX alone (CZP+MTX→MTX; n=108, PBO+MTX→MTX; n=71). Patients who flared could receive rescue treatment with open-label CZP.

Results 34 CZP+MTX→MTX patients and 14 PBO+MTX→MTX patients discontinued during the PT period. From week 52 through week 104, significant inhibition of total modified total Sharp score progression was observed for CZP+MTX versus PBO+MTX (week 104: 84.2% vs 67.5% (p<0.001)). Remission rates decreased after CZP discontinuation; however, higher rates were maintained through week 104 in CZP+MTX→MTX versus PBO+MTX→MTX (41.5% vs 29.3% (p=0.026), 34.6% vs 24.2% (p=0.049) and 41.5% vs 33.1% (p=0.132) at week 104 in SDAI, Boolean and DAS28(erythrocyte sedimentation rate) remission. CZP retreated patients due to flare (n=28) showed rapid clinical improvement. The incidence of overall adverse events was similar between groups.

Conclusions In MTX-naïve patients with early RA with poor prognostic factors, an initial 1 year of add-on CZP to 2-year optimised MTX therapy brings radiographic and clinical benefit through 2 years, even after stopping CZP.

Trial registration number NCT01451203.

  • Early Rheumatoid Arthritis
  • DMARDs (biologic)
  • Methotrexate
  • Anti-TNF

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Statistics from Altmetric.com

Footnotes

  • Handling editor Tore K Kvien

  • Contributors All authors were involved in the C-OPERA study, reviewed and interpreted the data, developed the manuscript and approved the final draft.

  • Funding Astellas Pharma. and UCB Pharma funded this study and manuscript.

  • Competing interests TA has taken part in speakers' bureaus for Astellas, Bristol-Myers, Chugai and Mitsubishi-Tanabe. KY has received consultancy fees from Abbott, BMS, Chugai, Eisai, Mitsubishi-Tanabe, Pfizer, Roche and UCB Pharma; and has received research grants from Abbott, Eisai, Mitsubishi-Tanabe, Pfizer, Santen and UCB Pharma. TT has received consultancy fees from AstraZeneca, Asahi Kasei, Eli Lilly, Mitsubishi-Tanabe and Novartis; research grants from Abbott, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe, Nippon Shinyaku, Otsuka, Pfizer, Sanofi-Aventis, Santen, Takeda and Teijin; and has taken part in speakers' bureaus for Abbott, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer and Takeda and UCB Pharma. HY has received consultancy fees from Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda and UCB Pharma; and has received research grants from Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda and UCB Pharma. NI has received research grants from Abbott, Astellas, BMS, Takeda, Chugai, Eisai, Janssen, Kaken Mitsubishi-Tanabe and Pfizer; and has taken part in speakers' bureaus for Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Kaken, Mitsubishi-Tanabe, Otsuka, Pfizer, Taisho-Toyama and Takeda. YT has received research grants from Astellas, Abbvie, BMS, Chugai, Daiichi-Sankyo, Mitsubishi-Tanabe, MSD; has received consultancy fees from Abbott, Abbvie, Asahi Kasei, Astellas, AstraZeneca, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, GSK, Janssen, Mitsubishi-Tanabe, MSD, Pfizer, Quintiles, Takeda and UCB Pharma; and has taken part in speakers' bureaus for Abbott, Abbvie, Asahi Kasei, Astellas, AstraZeneca, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, GSK, Janssen, Mitsubishi-Tanabe, MSD, Pfizer, Quintiles, Takeda and UCB Pharma. KE has received consultancy fees from UCB Pharma. AW has received research grants from Daiichi-Sankyo, Dainippon-Sumitomo, Kyorin, Meiji Seika; Shionogi, Taiho, Taisho and Toyama Chemical; and has taken part in speakers' bureaus for Daiichi-Sankyo, Dainippon-Sumitomo, GSK, Mitsubishi-Tanabe, MSD, Pfizer, Shionogi and Taisho-Toyama. HO has received consultancy fees from Astellas and UCB Pharma. SY has received research grant from BMS and taken part in speakers' bureaus for Abbvie, Astellas, Chugai, Eizai, Pfizer, Mitsubishi-Tanabe and Takeda. YY has no competing interests to disclose. YK has received speakers' bureau from Astellas, Chugai and Ono. TM has received speaker honoraria from Pfizer Japan, Janssen Pharmaceutical Co.. and Astellas Pharma; and research grants form Quintiles Transnational Japan K.K, Janssen Pharmaceutical Co., Takeda Chemical Industries, Daiichi Sankyo Co., Astellas Pharma, Eli Lilly Japan K.K., MSD Co., Nippon Kayaku Co., Parexel International, Pfizer Japan and Bristol-Myers Squibb. MI has received payment for lectures from Astellas, Chugai, Ono and Tanabe-Mitsubishi; has received research grants from Pfizer and a royalty fee from Chugai. TS is an employee of UCB Pharma; TO is an employee of Astellas. DvdH has received consultancy fees from Abbvie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi-Sankyo, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma and Vertex; and is the Director of Imaging Rheumatology bv. NM has received research grants from Abbott, Astellas, Chugai, Eisai, Mitsubishi-Tanabe, Pfizer and Takeda. TK has received consultancy fees from Abbvie, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Pfizer, Santen, Taisho-Toyama, Takeda, Teijin and UCB Pharma, and has taken part in speakers' bureaus for Abbott, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Pfizer, Santen, Taisho-Toyama, Takeda, Teijin and UCB Pharma.

  • Ethics approval This study was conducted after review and approval by the institutional review board designated by each study site after consideration of the ethical, scientific and medical justification for the conduct of the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.