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Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade
  1. J S Smolen1,2,
  2. C Han11,
  3. D M F M van der Heijde3,
  4. P Emery4,
  5. J M Bathon5,
  6. E Keystone6,
  7. R N Maini7,
  8. J R Kalden8,
  9. D Aletaha1,
  10. D Baker10,
  11. J Han10,
  12. M Bala11,
  13. E W St Clair9,
  14. for the Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) Study Group
  1. 1
    Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
  2. 2
    2nd Department of Medicine, Hietzing Hospital, Vienna, Austria
  3. 3
    Leiden University Medical Center, Leiden, The Netherlands
  4. 4
    Research School of Medicine, University of Leeds, Leeds, UK
  5. 5
    Johns Hopkins University, Baltimore, Maryland, USA
  6. 6
    Center for Advanced Therapeutics, Mount Sinai Hospital, Toronto, Canada
  7. 7
    Kennedy Institute of Rheumatology, London, UK
  8. 8
    Division for Molecular Immunology, Nikolaus-Fiebiger-Center, Erlangen, Germany
  9. 9
    Duke University Medical Center, Durham, North Carolina, USA
  10. 10
    Centocor Research and Development, Inc, Malvern, Pennsylvania, USA
  11. 11
    Johnson & Johnson Pharmaceutical Services, Worldwide Health Economics and Pricing, Malvern, Pennsylvania, USA
  1. Dr J S Smolen, Division of Rheumatology, Department of Medicine III, Medical University Vienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria; josef.smolen{at}


Objective: To examine the association of radiographic progression and disease activity states in patients with rheumatoid arthritis (RA) treated with methotrexate with or without infliximab.

Methods: Patients (n  =  1049) with active RA for 3 years or less and no previous methotrexate treatment were randomly assigned (4 : 5 : 5) to receive methotrexate plus placebo or methotrexate plus infliximab 3 or 6 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter to week 46. Disease activity was classified by the simplified disease activity index as remission (⩽3.3), low (>3.3 to ⩽11), moderate (>11 to ⩽26), high (>26). Radiographic progression was measured as a change from baseline to week 54 in total Sharp score.

Results: At weeks 14 and 54, more patients receiving methotrexate plus infliximab than methotrexate plus placebo were in remission (10.7% versus 2.8% week 14; 21.3% versus 12.3% week 54; p<0.001 for both). Methotrexate plus placebo halted radiographic progression only if patients achieved remission within 3 months, whereas methotrexate plus infliximab also halted or minimised progression in patients with low or moderate activity, respectively. Patients with persistently high disease activity levels had much less progression of joint damage if treated with methotrexate plus infliximab versus methotrexate monotherapy. Even with infliximab plus methotrexate there was a direct relationship between disease activity and radiographic changes, although the slope was deflected when compared with methotrexate monotherapy.

Conclusion: With methotrexate, joint damage progresses even at low and moderate disease activity levels, whereas methotrexate plus infliximab inhibits radiographic progression across all disease activity states.

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  • Competing interests: EWSC received grant support from Amgen. He is a consultant for Genentech, Bristol-Meyers Squibb, Novartis, Synovex, Biogen Idec and Medimmune. CH owns Johnson & Johnson stocks. JMB has research contracts with Amgen, Bristol Myers Squibb and IDEC-Biogen. PE has provided expert advice and undertaken clinical trials for Centocor/Schering-Plough, Amgen, Abbott and UCB. EK was funded by Abbott Laboratories, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Centocor, Inc, F Hoffmann-LaRoche Inc, Novartis Pharmaceuticals Corp, Schering-Plough Corporation, UCB and Wyeth Pharmaceuticals and is a consultant for Abbott Laboratories, Amgen Inc, Bristol-Myers Squibb Company, Centocor, Inc, Chelsea Therapeutics, Inc, CombinatoRx Inc, F Hoffmann-La Roche Inc, Genentech, Inc, GlaxoSmithKline, Medarex, Inc, Schering-Plough Corporation, UCB and Wyeth Pharmaceuticals. DMFMH has received consultancy fees and/or research grants from Abbott, Amgen, BMS, Centocor, Chugai, Roche, Schering Plough and UCB. RNM has had consultancies/advisory boards with Abbott Laboratories, Arana (formerly Peptech), AstraZeneca, Boehringer Ingelheim Ltd, Centocor Inc, Domantis, Evotec, F-star, GlaxoSmithKline, Nicholas Piramal India Ltd, Roche, Schering-Plough and UCB/Celltech in the past 5 years. The inventor’s shares of royalties are received by Kennedy Institute of Rheumatology Trust from Centocor and Abbott. JRK has served on advisory boards of Abbott, Wyeth, Centocor, Pfizer and Merck. JSS received grant support from Abbott, Roche, UCB, Schering-Plough, Wyeth and honoraria from Abbott, Amgen, Astra-Zeneca, BMS, Centocor, Novartis, Roche, Schering-Plough, UCB, Wyeth.

  • Funding: This research was supported by Centocor, Inc, Malvern, PA, a subsidiary of Johnson & Johnson.

  • Ethics approval: The protocol was approved by an institutional review board at each study centre and carried out according to the Helsinki Declaration of 1975, as revised in 1983 and 1989.

  • Patient consent: Obtained.

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