Objectives To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks.
Methods DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints.
Results Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): −1.00 vs −0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY).
Conclusions CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.
Trial registration number NCT01519791.
- Early Rheumatoid Arthritis
- DMARDs (biologic)
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Handling editor Tore K Kvien
Correction notice This article has been corrected since it was published Online First. In the penultimate paragraph of the Discussion section the ‘IR of SIEs with CZP+MTX in this study’ has been corrected to ‘(3.3/100 PY)’.
Contributors All the authors made substantial contributions to the evaluation of the study results and to the development and review of the manuscript.
Funding UCB Pharma sponsored the study and the development of the manuscript. In addition to content approval by the authors, UCB signed off on the manuscript following a full review to ensure that the data presented in the publication are scientifically, technically and medically supportable and did not contain any information which has the potential to damage the intellectual property of UCB. Additionally, UCB ensured that the publication complies with applicable laws, regulations, guidelines and good industry practice.
Competing interests PE received consultancy and speaker's fee from Pfizer, MSD, AbbVie, UCB Pharma, Roche, Bristol-Myers Squibb, Schering-Plough, Novartis and Samsung. COBIII received consultancy fees from UCB Pharma. GRB received consultancy fees from AbbVie, MSD, Pfizer, Roche and UCB Pharma. DEF received research grants from Abbott, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech and UCB Pharma; consultancy fees from Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen IDEC, Janssen, Gilead, GlaxoSmithKline, NIH, Novartis, Pfizer, Roche/Genentech and UCB Pharma and other fees from Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen, IDEC, Janssen, Gilead, NIH, Roche/Genentech, Abbott, Actelion and UCB Pharma. XM received research grants from Pfizer, GlaxoSmithKline and Roche and consultancy fees from Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, UCB Pharma and Sanofi-Aventis. DvdH received consultancy fees from AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma and Vertex; research grants from AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma and Vertex and is Director of Imaging at Rheumatology BV. RvV received research support from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche and UCB Pharma and consultancy fees from AbbVie, Biotest, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Eli-Lilly, Merck, Pfizer, Roche, UCB Pharma and Vertex. CA is an employee of UCB Pharma. IM is an employee of UCB Pharma. OP is an employee of UCB Pharma. DT is an employee of UCB Pharma. BV is an employee of UCB Pharma. MEW received research grants from Amgen, Bristol-Myers Squibb, Crescendo Bioscience and UCB Pharma and consultancy fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, Eli-Lilly, MedImmune, Merck, Novartis, Pfizer, Roche and UCB Pharma.
Ethics approval This study was conducted in accordance with the current version of the applicable regulatory and International Conference on Harmonisation (ICH)-Good Clinical Practice (GCP) requirements, the ethical principles that have their origin in the principles of the Declaration of Helsinki and the local laws of the countries involved.
Provenance and peer review Not commissioned; externally peer reviewed.