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Open-label, pilot protocol of patients with rheumatoid arthritis who switch to infliximab after an incomplete response to etanercept: the opposite study
  1. Daniel E Furst1,
  2. Norman Gaylis2,
  3. Vance Bray3,
  4. Ewa Olech4,
  5. David Yocum5,
  6. Jeffrey Ritter6,
  7. Michael Weisman7,
  8. Daniel J Wallace8,
  9. John Crues9,
  10. Dinesh Khanna1,
  11. Gregory Eckel10,
  12. Newman Yeilding11,
  13. Peter Callegari11,
  14. Sudha Visvanathan11,
  15. Jeannie Rojas11,
  16. Ronald Hegedus11,
  17. Laura George11,
  18. Khalid Mamun11,
  19. Keith Gilmer11,
  20. Orrin Troum12
  1. 1Division of Rheumatology, Department of Medicine, University of California Los Angeles, Los Angeles, California, USA
  2. 2Arthritis and Rheumatic Disease Specialties, Aventura, Florida, USA
  3. 3Denver Arthritis Clinic, Denver, Colorado, USA
  4. 4Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA
  5. 5University of Arizona Health Sciences Center, Tucson, Arizona, USA
  6. 6Center for Arthritis and Rheumatology, South Miami, Florida, USA
  7. 7Cedars-Sinai Medical Center, Division of Rheumatology, Los Angeles, California, USA
  8. 8Wallace Rheumatic Study Center, Los Angeles, California, USA
  9. 9Pronet Imaging, Los Angeles, California, USA
  10. 10Department of Radiological Sciences, University of California Los Angeles, Torrance, California, USA
  11. 11Centocor, Malvern, Pennsylvania, USA
  12. 12Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  1. Correspondence to:
    Dr D E Furst
    Division of Rheumatology, Department of Medicine, University of California Los Angeles,32–59 Rehabilitation Center, 1000 Veteran Avenue, Los Angeles, CA 90095–1670, USA;DEFurst{at}mednet.ucla.edu

Abstract

Objective: To incorporate a new trial design to examine clinical response, cytokine expression and joint imaging in patients with rheumatoid arthritis (RA) switching from etanercept to infliximab treatment.

Methods: A randomised, open-label, clinical trial of 28 patients with an inadequate response to etanercept was conducted. Eligible patients received background methotrexate and were randomised 1:1 to discontinue etanercept and receive infliximab 3 mg/kg at weeks 0, 2, 6, 14 and 22, or to continue etanercept 25 mg twice weekly. Data were analysed for clinical response, serum biomarker levels, radiographic progression, MRI and adverse events.

Results: At week 16, 62% of infliximab-treated patients achieved American College of Rheumatology 20% criteria for improvement in RA (ACR20) responses compared with 29% of etanercept-treated patients. A 30.8% decrease from baseline in Disease Activity Score 28 was observed in patients receiving infliximab, compared with a 16.0% decrease in patients receiving etanercept. ACR20 and American College of Rheumatology 50% criteria for improvement in RA responses correlated at least minimally with intracellular adhesion molecule-1 and interleukin 8 in patients receiving infliximab. 38% of patients who were switched to infliximab showed reductions in Health Assessment Questionnaire scores (>0.4), compared with 0% of patients receiving etanercept. MRI analyses were inconclusive. Both drugs were well tolerated; 54% of infliximab-treated patients and 50% of etanercept-treated patients reported adverse events.

Conclusions: In this exploratory, open-label trial (with single-blind evaluator), patients were randomised to continue with etanercept or switch to infliximab. The small sample size of this hypothesis-generating study was underpowered to show statistical differences between groups. There was a numerical trend favouring patients who switched to infliximab, therefore warranting further study with a more rigorous design.

  • ACR, American College of Rheumatology
  • ACR20, ACR 20% criteria for improvement in RA
  • ACR50, ACR 50% criteria for improvement in RA
  • COL 2–3/4C long neoepitope, type II collagen cleavage by collagenase
  • CTX-1, C-telopeptide-1
  • DAS28, Disease Activity Score 28
  • HAQ, Health Assessment Questionnaire
  • ICAM-1, intracellular adhesion molecule-1
  • IL, interleukin
  • MMP-3, matrix metalloproteinase-3
  • MTX, methotrexate
  • RA, rheumatoid arthritis
  • SHS, Sharp score with the van der Heijde modification
  • SJC, swollen joint count
  • TJC, tender joint count
  • TNFα, tumour necrosis factor alpha
  • VEGF, vascular endothelial growth factor
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Footnotes

  • Published Online First 5 April 2007

  • Funding: This study was funded by Centocor, Malvern, Pennsylvania, USA.

  • Competing interests: DEF received grants from Amgen, Abbott, Centocor, Genentech, Roche, NIH, Novartis, Genmab and Merck, and consulting fees from Amgen, Abbott, Genentech, Roche, NIH, Novartis and Merck. NG was a consultant at the time of the study for Centocor and MagneVu. VB received grants from Amgen and Centocor. EO received grants from Amgen, Bristol-Myers Squibb, Centocor, F Hoffmann-La Roche, Genentech, Human Genome Sciences, MedImmune, Otsuka America Pharmaceutical, speaking fees from Abbott, Centocor and MagneVu, and consulting fees from Abbott, Genentech and MagneVu. DY received grants and speaking fees from Centocor, Amgen and Abbott, and advising fees from Centocor. JR received consulting fees from Genentech and Biogenidec. MW received grants from Abbott, Actelion Pharmaceuticals, Amgen, Aspreva Pharmaceutical, BioRad Laboratories, Bristol Myers Squibb, Centocor, Genentech, Eli Lilly, Human Genome Sciences, Immunex, Immunomedics, Merck, Novartis, Pfizer, Procter and Gamble, Protein Design Labs, Sanofi Aventis, TAP Pharmaceuticals and Wyeth, and consulting fees from Abbott, Amgen, Bristol Myers, Elan Pharmaceuticals, Human Genome Sciences, Merck, Vertex Pharmaceuticals and Wyeth. DJW has no competing interests. J C owns stock in MagneVu. DK received grants from TAP Pharmaceuticals, speaking fees from Abbott, Wyeth, Amgen and Actelion Pharmaceuticals, and consulting fees from Centocor. GE has no competing interests. NY, PC, SV, JR, RH, LG, KM and KG are employees of Centocor. NY, SV, RH and LG own stock in Centocor. OT received grants, speaking fees and consulting fees from Centocor, Amgen and Wyeth.

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