PMID- 27165179
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20220331
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Print)
IS  - 0003-4967 (Linking)
VI  - 76
IP  - 1
DP  - 2017 Jan
TI  - Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naive 
      patients with early, active rheumatoid arthritis with poor prognostic factors: 
      1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase 
      III study.
PG  - 96-104
LID - 10.1136/annrheumdis-2015-209057 [doi]
AB  - 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-naive patients with 
      moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor 
      prognostic factors over 52 weeks. METHODS: DMARD-naive 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-naive 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.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://www.bmj.com/company/products-services/rights-and-licensing/.
FAU - Emery, P
AU  - Emery P
AD  - Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, 
      Leeds, UK.
AD  - NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS 
      Trust, Leeds, UK.
FAU - Bingham, C O 3rd
AU  - Bingham CO 3rd
AD  - Johns Hopkins University, Baltimore, Maryland, USA.
FAU - Burmester, G R
AU  - Burmester GR
AD  - Rheumatology and Clinical Immunology, Charite-University Medicine, Berlin, 
      Germany.
FAU - Bykerk, V P
AU  - Bykerk VP
AD  - Division of Rheumatology, Weill Cornell Medical College, Hospital for Special 
      Surgery, New York, New York, USA.
FAU - Furst, D E
AU  - Furst DE
AD  - Division of Rheumatology, David Geffen School of Medicine at UCLA, Los Angeles, 
      California, USA.
FAU - Mariette, X
AU  - Mariette X
AD  - Universite Paris-Sud, Hopitaux Universitaires Paris-Sud, AP-HP, Le Kremlin 
      Bicetre, France.
FAU - van der Heijde, D
AU  - van der Heijde D
AUID- ORCID: 0000-0002-5781-158X
AD  - Deprtment of Rheumatology, Leiden University Medical Centre, Leiden, The 
      Netherlands.
FAU - van Vollenhoven, R
AU  - van Vollenhoven R
AD  - Unit for Clinical Therapy Research, Inflammatory Disease, Karolinska Institute, 
      Stockholm, Sweden.
FAU - Arendt, C
AU  - Arendt C
AD  - UCB Pharma, Brussels, Belgium.
FAU - Mountian, I
AU  - Mountian I
AD  - UCB Pharma, Brussels, Belgium.
FAU - Purcaru, O
AU  - Purcaru O
AD  - UCB Pharma, Brussels, Belgium.
FAU - Tatla, D
AU  - Tatla D
AD  - UCB Pharma, Raleigh, North Carolina, USA.
FAU - VanLunen, B
AU  - VanLunen B
FAU - Weinblatt, M E
AU  - Weinblatt ME
AD  - UCB Pharma, Raleigh, North Carolina, USA.
AD  - Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01519791
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20160510
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Antirheumatic Agents)
RN  - UMD07X179E (Certolizumab Pegol)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
CIN - Ann Rheum Dis. 2016 Oct;75(10):e68. PMID: 27390362
CIN - Ann Rheum Dis. 2016 Oct;75(10):e69. PMID: 27519773
MH  - Adult
MH  - Antirheumatic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Arthritis, Rheumatoid/diagnostic imaging/*drug therapy
MH  - Certolizumab Pegol/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Drug Therapy, Combination/adverse effects
MH  - Female
MH  - Humans
MH  - Infections/chemically induced
MH  - Male
MH  - Methotrexate/administration & dosage/adverse effects/*therapeutic use
MH  - Middle Aged
MH  - Prognosis
MH  - Radiography
MH  - Remission Induction
PMC - PMC5264210
OTO - NOTNLM
OT  - Anti-TNF
OT  - DMARDs (biologic)
OT  - Early Rheumatoid Arthritis
OT  - Methotrexate
COIS- 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.
EDAT- 2016/05/12 06:00
MHDA- 2017/06/07 06:00
PMCR- 2017/01/25
CRDT- 2016/05/12 06:00
PHST- 2015/12/18 00:00 [received]
PHST- 2016/04/08 00:00 [revised]
PHST- 2016/04/09 00:00 [accepted]
PHST- 2016/05/12 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2016/05/12 06:00 [entrez]
PHST- 2017/01/25 00:00 [pmc-release]
AID - annrheumdis-2015-209057 [pii]
AID - 10.1136/annrheumdis-2015-209057 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2017 Jan;76(1):96-104. doi: 10.1136/annrheumdis-2015-209057. Epub 
      2016 May 10.