Article Text

PDF
THU0192 5-Year Results from the Rapid 1 Trial and Open-Label Extension: Long-Term Safety and Efficacy of Certolizumab Pegol in Combination with Methotrexate in the Treatment of Rheumatoid Arthritis
  1. E. Keystone1,
  2. R. Landewé2,
  3. R. van Vollenhoven3,
  4. B. Combe4,
  5. V. Strand5,
  6. P. J. Mease6,
  7. L. Shaughnessy7,
  8. B. VanLunen7,
  9. D. van der Heijde8
  1. 1University of Toronto, Toronto, Canada
  2. 2University Hospital Maastricht, Maastricht, Netherlands
  3. 3Karolinska Institute, Stockholm, Sweden
  4. 4Montpellier University Hospital, Montpellier, France
  5. 5Stanford University, Palo Alto
  6. 6Swedish Medical Center and University of Washington, Seattle
  7. 7UCB Pharma, Raleigh, United States
  8. 8Leiden University Medical Center, Leiden, Netherlands

Abstract

Background In the RAPID 1 randomized clinical trial (RCT; NCT00152386),1 certolizumab pegol (CZP) every 2 weeks (Q2W) plus MTX over 52 weeks (wks) provided rapid improvements in signs and symptoms and inhibition of radiographic damage in patients (pts) with active rheumatoid arthritis (RA).

Objectives To examine the safety and efficacy of CZP plus MTX over 5 yrs in RA.

Methods Eligible pts were treated in the open-label extension (OLE) to RAPID 1 (NCT00175877) with CZP 400mg Q2W, reduced to 200mg Q2W after ≥6 months, plus MTX.2 Primary objective of the OLE was to monitor safety; secondary objective was to assess efficacy. Combined safety data from RCT and OLE are presented to Wk334 (6.4 yrs) from first dose of CZP for all pts receiving ≥1 dose of CZP in OLE (Safety population, N=846). Pt retention and efficacy data are presented to Wk256 (4.9 yrs) for CZP pts who completed the 52-wk RCT (CZP completers, N=507) and for all pts randomized to CZP 400mg or 200mg in RCT (ITT population, N=783). Efficacy was assessed by ACR20/50/70, DAS28(ESR) and HAQ-DI. Missing categorical data were imputed by non-responder imputation (NRI). Continuous measures were imputed by last observation carried forward (LOCF). Kaplan-Meier analysis was used to estimate pt retention.

Results Overall event rate per 100 pt-yrs (ER) of AEs was 285.6 and SAEs was 18.4 (infections=5.4, malignancies=1.0; total exposure [including 84-day safety follow-up period]: 3,660 pt-yrs). The most common AEs (MedDRA preferred terms) were urinary tract infection (ER=7.8), nasopharyngitis (ER=7.4) and upper respiratory tract infection (ER=7.3). 137 pts (16.2%) experienced an AE leading to withdrawal (incidence rate per 100 pt-yrs [IR]=3.77). 16 (1.9%) experienced an AE leading to death (IR=0.44) (including 4 malignancies, 3 infections, 2 cardiovascular events). ACR20/50/70 response rates for CZP completers and ITT population were sustained to Wk256 (74.6%/57.4%/39.6% and 59.0%/43.7%/28.8%, respectively), as were DAS28(ESR) remission rates (25.2% and 20.3%), improvements in DAS28(ESR) (mean values: 3.43 and 3.83; mean change from baseline: -3.49 and -3.08) and HAQ-DI (mean values: 0.90 and 1.00; mean change from baseline: -0.77 and -0.66).

Conclusions CZP plus MTX provided a favorable risk-benefit profile over 5 yrs of treatment in pts with active RA. No new safety signals were identified.

References

  1. Keystone E. Arthritis Rheum 2008;58(11):3319-3329,

  2. Keystone E. Rheumatology 2012;51(9):1628-1638

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

Disclosure of Interest E. Keystone Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, F. Hoffmann-La Roche, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, AstraZeneca, Biotest, BMS, F. Hoffmann-La Roche, Genetech, Janssen, Lilly, Merck, Nycomed, Pfizer, UCB Pharma, Speakers bureau: Abbott, Amgen, AstraZeneca, BMS Canada, F. Hoffmann-La Roche, Janssen, Pfizer, UCB Pharma, R. Landewé Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, Consultant for: Abbott, Ablynx, Amgen, AstraZeneca, BMS, Centocor, GSK, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, Speakers bureau: Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, R. van Vollenhoven Grant/research support from: Abbott, BMS, GSK, MSD, Pfizer, Roche, UCB Pharma, Consultant for: Abbott, BMS, GSK, MSD, Pfizer, Roche, UCB Pharma, B. Combe Grant/research support from: Merck, Pfizer, Roche-Chugai, Consultant for: Merck, Pfizer, Roche-Chugai, UCB Pharma, BMS, Celgene, Lilly, Novartis, Speakers bureau: Merck, Pfizer, Roche-Chugai, UCB Pharma, BMS, Celgene, Lilly, Novartis, V. Strand Consultant for: UCB Pharma, P. Mease Grant/research support from: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Speakers bureau: Abbott, Amgen, BiogenIdec, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, L. Shaughnessy Employee of: UCB Pharma, B. VanLunen Employee of: UCB Pharma, D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, Vertex, Employee of: Imaging Rheumatology bv

Statistics from Altmetric.com

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.