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SAT0164 The First Study of Certolizumab Pegol in Combination with Methotrexate in Dmard-Naïve Early Rheumatoid Arthritis Patients Led to Sustained Clinical Response and Inhibition of Radiographic Progression at 52 Weeks: The C-Early Randomized, Double-Blind, Controlled Phase 3 Study
  1. P. Emery1,
  2. C.O. Bingham2,
  3. G.-R. Burmester3,
  4. V.P. Bykerk4,
  5. D.E. Furst5,
  6. X. Mariette6,
  7. D. van der Heijde7,
  8. D. Tatla8,
  9. C. Arendt9,
  10. I. Mountian9,
  11. B. VanLunen8,
  12. M. Weinblatt10
  1. 1University of Leeds, Leeds, United Kingdom
  2. 2John Hopkins University, Baltimore, United States
  3. 3Charité - University Medicine Berlin, Berlin, Germany
  4. 4Weill Cornell Medical College, Hospital for Special Surgery, New York
  5. 5University of California, Los Angeles, United States
  6. 6Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, Paris, France
  7. 7Leiden University Medical Centre, Leiden, Netherlands
  8. 8UCB Pharma, Raleigh, United States
  9. 9UCB Pharma, Brussels, Belgium
  10. 10Brigham and Women's Hospital, Boston, United States

Abstract

Background C-EARLY is a phase 3 study in DMARD-naïve patients (pts) with early active RA.

Objectives To assess efficacy and safety of certolizumab pegol (CZP)+MTX vs placebo (PBO)+MTX treatment in inducing and maintaining sustained clinical response and inhibiting radiographic damage in DMARD-naïve pts with early active RA.

Methods Eligible pts in this multicenter, double-blind, randomized study (NCT01519791) were DMARD-naïve and had early, active RA:<1 year since diagnosis at baseline (BL) fulfilling 2010 ACR/EULAR criteria; ≥4 swollen and ≥4 tender joints; DAS28(ESR)≥3.2; CRP≥10mg/L and/or ESR≥28mm/hr, rheumatoid factor or ACPA positive. Pts were randomized 3:1 to CZP (400mg Wks 0,2,4 then 200mg every 2 wks to Wk52)+MTX or PBO+MTX. MTX was initiated at 10mg/wk and up to 25mg/wk by Wk8, maximum tolerated dose was maintained to Wk52. Primary endpoint was sustained DAS28(ESR) remission (sREM, DAS28[ESR]≤2.6 at Wk40 and Wk52) and key secondary endpoint was sustained low disease activity (sLDA) (DAS28[ESR]≤3.2 at Wk40 and Wk52). Other secondary endpoints (included in hierarchical testing) were Wk52 ACR50 response, change from BL in HAQ-DI and change from BL in van der Heijde modified total Sharp score (mTSS).

Results 660 (CZP+MTX) and 219 (PBO+MTX) pts were randomized. 655 vs 213 were included in full analysis set (FAS; pts with BL and post-BL DAS28[ESR]) and 528 vs 163 in radiographic analysis set (FAS pts with valid BL and post-BL radiographs), respectively. BL characteristics were balanced between arms. 96.5% pts had high disease activity (DAS28[ESR]>5.1), 77.8% had erosions; mean TJC and SJC 15.8 and 12.5, respectively. Mean MTX dose after Wk8 was 21.1 (CZP+MTX) and 22.3 (PBO+MTX) mg/wk. Primary (sREM) and secondary endpoints in hierarchical testing (sLDA, ACR50, HAQ-DI change from BL, mTSS change from BL) were statistically significant (Figure shows all except HAQ-DI LS mean change from BL, -1.00 vs -0.82, p<0.001). Lower Erosion Score, Joint Space Narrowing (Figure) and higher proportion of pts with mTSS non-progression (70.3% vs 49.7%) were seen with CZP+MTX vs PBO+MTX. AE incidence rates were similar for both arms. Infections were higher with CZP+MTX (71.8 [CZP+MTX] vs 52.7 [PBO+MTX]/100 pt-yrs), but similar for serious infections (3.3 vs 3.7/100 pt-yrs). 2 deaths were reported with CZP+MTX (1 stroke; 1 systemic tuberculosis); 1 with PBO+MTX (respiratory failure). No new safety signals for CZP were reported.

Conclusions This first report of efficacy and safety of CZP+MTX in DMARD-naïve early RA showed CZP+MTX resulted in more pts in sREM and sLDA; greater improvements in RA signs and symptoms including physical function; and inhibition of structural damage compared with PBO+MTX. Safety profile of CZP+MTX was similar to PBO+MTX.

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

Disclosure of Interest P. Emery Consultant for: Pfizer, MSD, AbbVie, UCB Pharma, Roche and BMS, Speakers bureau: Pfizer, MSD, AbbVie, UCB Pharma, Roche and BMS, C. Bingham: None declared, G.-R. Burmester: None declared, V. Bykerk: None declared, D. Furst Grant/research support from: Abbott, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB Pharma, Consultant for: Abbott, Actelion, Amgen, Bristol-Myers Squibb, BiogenIdec, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB Pharma, Speakers bureau: Abbott, Actelion, UCB Pharma, X. Mariette Grant/research support from: Pfizer, Roche, Consultant for: BMS, GSK, Pfizer, Roche, UCB Pharma, 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, D. Tatla Employee of: UCB Pharma, C. Arendt Employee of: UCB Pharma, I. Mountian Employee of: UCB Pharma, B. VanLunen Employee of: UCB Pharma, M. Weinblatt Grant/research support from: Bristol Myers Squibb, Crescendo Bioscience, UCB Pharma, Consultant for: Amgen, Abbvie, Bristol Myers Squibb, Crescendo Bioscience, UCB Pharma, Roche

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