Article Text
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
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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.