Seminars in Arthritis and Rheumatism
Volume 39, Issue 2 , Pages 123-131 , October 2009

Treatment with Infliximab plus Methotrexate Improves Anemia in Patients with Rheumatoid Arthritis Independent of Improvement in Other Clinical Outcome Measures—A Pooled Analysis from Three Large, Multicenter, Double-Blind, Randomized Clinical Trials

  • Mittie K. Doyle, MD

      Affiliations

    • Associate Director, Immunology, Clinical Research and Development, Centocor Inc., Malvern, PA; Adj. Assistant Professor, University of Pennsylvania School of Medicine, Rheumatology, Philadelphia, PA
    • Corresponding Author InformationAddress reprints requests to: Mittie K. Doyle, MD, 200 Great Valley Parkway, Centocor, Inc., Malvern, PA 19355
    • ,
  • Mahboob U. Rahman, MD, PhD

      Affiliations

    • Senior Director Immunology, Clinical Research and Development, Centocor Research and Development, Inc., Malvern, PA; Adj. Associate Professor, University of Pennsylvania School of Medicine, Rheumatology, Philadelphia, PA
    • ,
  • Chenglong Han, PhD

      Affiliations

    • Associate Director, Health Economic Administration, Centocor Research and Development, Inc., Malvern, PA
    • ,
  • John Han, PhD

      Affiliations

    • Director, Biostatistics, Centocor Research and Development, Inc., Malvern, PA
    • ,
  • Jon Giles, MD

      Affiliations

    • Assistant Professor of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, MD
    • ,
  • Clifton O. Bingham III, MD

      Affiliations

    • Assistant Professor of Medicine, Division of Rheumatology and Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, MD
    • ,
  • Joan Bathon, MD

      Affiliations

    • Director, Arthritis Center and Professor of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, MD

References 

  1. Wolfe F, Michaud K. Anemia and renal function in patients with rheumatoid arthritis. J Rheumatol. 2006;33:1516–1522
  2. Revicki DA, Brown RE, Feeny DH, Henry D, Teehan BP, Rudnick MR, et al. Health- related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients. Am J Kidney Dis. 1995;25:548–554
  3. Glaspy J, Bukpwski Bukowski R, Steinberg D, Taylor C, Tchekmedyian S, Vadhan-Raj S Procrit Study Group. Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. J Clin Oncol. 1997;15:1218–1234
  4. Littlewood TJ, Bajetta E, Nortier JW, Vercammen E, Rapoport B Epoetin Alfa Study Group. Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double blind, placebo-controlled trial. J Clin Oncol. 2001;19:2865–2874
  5. Peeters HR, Jongen-Lavrencic M, Bakker CH, Vreugdenhil G, Breedveld FC, Swaak AJ. Recombinant human erythropoietin improves health-related quality of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures. Rheumatol Int. 1999;18:201–206
  6. Nordström D, Lindroth Y, Marsal L, Hafstrom I, Henrich C, Rantapaa-Dahlqvist S, et al. Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis. Rheumatol Int. 1997;17:67–73
  7. Kaltwasser JP, Kessler U, Gottschalk R, Stucki G, Moller B. Effect of recombinant human erythropoietin and intravenous iron on anemia and disease activity in rheumatoid arthritis. J Rheumatol. 2001;28:2430–2436
  8. Murphy EA, Bell AL, Wojtulewski J, Brzeski M, Madhok R, Capell HA. Study of erythropoietin in treatment of anaemia in patients with rheumatoid arthritis. BMJ. 1994;309:1337–1338
  9. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011–1023
  10. Papadaki HA, Kritikos HD, Valatas V, Boumpas DT, Eliopoulos GD. Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti-tumor necrosis factor alpha therapy. Blood. 2002;100:474–482
  11. Jongen-Lavrencic M, Peeters HR, Wognum A, Vreugdenhil G, Breedveld FC, Swaak AJ. Elevated levels of inflammatory cytokines in bone marrow of patients with rheumatoid arthritis and anemia of chronic disease. J Rheum. 1997;24:1504–1509
  12. Vreugdenhil G, Lowenberg B, van Eijk HG, Swaak AJ. Tumor necrosis factor is associated with disease activity and the degree of anemia in patients with rheumatoid arthritis. Eur J Clin Invest. 1992;22:488–493
  13. Jongen-Lavrencic M, Peeters HR, Backx B, Touw IP, Vreugdenhil G, Swaak AJ. R-h-erythropoietin counteracts the inhibition of in vitro erythropoiesis by tumour necrosis factor alpha in patients with rheumatoid arthritis. Rheumatol Int. 1994;14:109–113
  14. Gudbjörnsson B, Hällgren R, Wide L, Birgegård G. Response of anaemia in rheumatoid arthritis to treatment with subcutaneous recombinant human erythropoietin. Ann Rheum Dis. 1992;51:747–752
  15. Pettersson T, Rosenlof K, Friman C, Mickos A, Teppo AM, Fyhrquist F. Successful treatment of anemia of rheumatoid arthritis with subcutaneously administered recombinant human erythropoietin (Slower response in patients with more severe inflammation). Scand J Rheumatol. 1993;22:188–193
  16. Davis D, Charles PJ, Potter A, Feldmann M, Maini RN, Elliott MJ. Anaemia of chronic disease in rheumatoid arthritis: in vivo effects of tumour necrosis factor alpha blockade. Br J Rheumatol. 1997;36:950–956
  17. Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, et al. ATTRACT Study Group Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomized phase III trial. Lancet. 1999;354:1932–1939
  18. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, et al. ATTRACT Study Group Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med. 2000;343:1594–1602
  19. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Furst D, Weisman MH, et al. ATTRACT Study Group Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum. 2004;50:1051–1065
  20. St Clair EW, van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P, et al. ASPIRE Study Group Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004;50:3432–3443
  21. Westhovens R, Yocum D, Han J, Berman A, Strusberg I, Geusens P, et al. START Study Group The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis with various comorbidities: a large, randomized, placebo-controlled trial. Arthritis Rheum. 2006;54:1075–1086
  22. Joy MS. Darbepoetin alfa: a novel erythropoiesis-stimulating protein. Ann Pharmacother. 2002;36:1183–1192
  23. Conover WJ. Practical nonparametric statistics. 2nd ed.. New York: John Wiley & Sons, Inc; 1980;
  24. DAS-Score N. Home of the DAS. Department of Rheumatology, University Medical Centre, Nijmegen-the Netherlands. http://www.reuma-nijmegen.nl/www.das-score.nl
  25. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36) (I. Conceptual framework and item selection). Med Care. 1992;30:473–483
  26. Han C, Rahman MU, Doyle MK, Bathon JM, Smolen J, Kavanaugh A, et al. Association of anemia and physical disability among patients with rheumatoid arthritis. J Rheumatol. 2007;34:2177–2182
  27. Roy CN, Andrews NC. Anemia of inflammation: the hepcidin link. Curr Opin Hematol. 2005;12:107–111
  28. Goodnough LT, Nissenson AR. Anemia and its clinical consequences in patients with chronic diseases. Am J Med. 2004;116:1S–2S
  29. Besarab A, Kline Bolton W, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998;339:584–590
  30. Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. 2006;98:708–714

 This research was supported by Centocor, Inc., Malvern, PA, USA, a subsidiary of Johnson & Johnson, New Brunswick, NJ. Drs. Doyle, Rahman, Han, and Han are employees of Centocor, Inc. and own stock in Johnson and Johnson. Drs. Giles, Bingham, and Bathon received consulting fees or research grants from Centocor, Inc.

PII: S0049-0172(08)00134-0

doi: 10.1016/j.semarthrit.2008.08.002

Seminars in Arthritis and Rheumatism
Volume 39, Issue 2 , Pages 123-131 , October 2009

Article Tools

* Image Usage & Resolution