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Ann Rheum Dis. Nov 2003; 62(Suppl 2): ii13–ii16.
PMCID: PMC1766753

Comparison of the efficacy of the tumour necrosis factor α blocking agents adalimumab, etanercept, and infliximab when added to methotrexate in patients with active rheumatoid arthritis


Objective: To determine, using the method of adjusted indirect comparisons, whether there are differences in efficacy of tumour necrosis factor (TNFα) blocking agents, as measured by the rate ratios for American College of Rheumatology (ACR) 20, 50, and 70 responses, in patients with rheumatoid arthritis with an incomplete response to methotrexate.

Methods: A systematic review was performed to identify placebo controlled trials of 24–30 weeks' duration of combination therapy that used a step-up approach with the addition of TNFα blocking agents to methotrexate. The method of "adjusted indirect comparisons" was used to compare results across trials to determine the relative risk for an ACR20 or 50 response.

Results: Placebo controlled trials for adalimumab, etanercept, and infliximab provided data on ACR20 and 50 responses. Both the similarity of demographic and disease characteristics of patients at entry, and the homogeneity of response rates in the placebo groups across trials, suggested that comparing results across trials was valid. The relative risk for obtaining an ACR20 and 50 response derived from the adjusted indirect comparisons of the TNFα blocking agents did not significantly differ from unity.

Conclusion: The analysis showed that the three currently marketed TNFα blocking agents have similarly efficacy when added to methotrexate in the treatment of patients with rheumatoid arthritis with active disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am. 2001 May;27(2):269–281. [PubMed]
  • Rasch Elizabeth K, Hirsch Rosemarie, Paulose-Ram Ryne, Hochberg Marc C. Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum. 2003 Apr;48(4):917–926. [PubMed]
  • Weinblatt ME, Coblyn JS, Fox DA, Fraser PA, Holdsworth DE, Glass DN, Trentham DE. Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med. 1985 Mar 28;312(13):818–822. [PubMed]
  • Williams HJ, Willkens RF, Samuelson CO, Jr, Alarcón GS, Guttadauria M, Yarboro C, Polisson RP, Weiner SR, Luggen ME, Billingsley LM, et al. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum. 1985 Jul;28(7):721–730. [PubMed]
  • Kremer JM. Safety, efficacy, and mortality in a long-term cohort of patients with rheumatoid arthritis taking methotrexate: followup after a mean of 13.3 years. Arthritis Rheum. 1997 May;40(5):984–985. [PubMed]
  • Weinblatt ME, Maier AL, Fraser PA, Coblyn JS. Longterm prospective study of methotrexate in rheumatoid arthritis: conclusion after 132 months of therapy. J Rheumatol. 1998 Feb;25(2):238–242. [PubMed]
  • Osman A, Mulherin D. Is parenteral methotrexate worth trying? Ann Rheum Dis. 2001 Apr;60(4):432–432. [PMC free article] [PubMed]
  • Verhoeven AC, Boers M, Tugwell P. Combination therapy in rheumatoid arthritis: updated systematic review. Br J Rheumatol. 1998 Jun;37(6):612–619. [PubMed]
  • Hochberg MC, Tracy JK, Flores RH. "Stepping-up" from methotrexate: a systematic review of randomised placebo controlled trials in patients with rheumatoid arthritis with an incomplete response to methotrexate. Ann Rheum Dis. 2001 Nov;60 (Suppl 3):iii51–iii54. [PMC free article] [PubMed]
  • Rau R. Adalimumab (a fully human anti-tumour necrosis factor alpha monoclonal antibody) in the treatment of active rheumatoid arthritis: the initial results of five trials. Ann Rheum Dis. 2002 Nov;61 (Suppl 2):ii70–ii73. [PMC free article] [PubMed]
  • Boers M, Tugwell P, Felson DT, van Riel PL, Kirwan JR, Edmonds JP, Smolen JS, Khaltaev N, Muirden KD. World Health Organization and International League of Associations for Rheumatology core endpoints for symptom modifying antirheumatic drugs in rheumatoid arthritis clinical trials. J Rheumatol Suppl. 1994 Sep;41:86–89. [PubMed]
  • Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B, Furst D, Goldsmith C, Kieszak S, Lightfoot R, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum. 1993 Jun;36(6):729–740. [PubMed]
  • Felson DT, Anderson JJ, Lange ML, Wells G, LaValley MP. Should improvement in rheumatoid arthritis clinical trials be defined as fifty percent or seventy percent improvement in core set measures, rather than twenty percent? Arthritis Rheum. 1998 Sep;41(9):1564–1570. [PubMed]
  • Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol. 1997 Jun;50(6):683–691. [PubMed]
  • Song Fujian, Altman Douglas G, Glenny Anne-Marie, Deeks Jonathan J. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ. 2003 Mar 1;326(7387):472–472. [PMC free article] [PubMed]
  • Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999 Dec 4;354(9194):1932–1939. [PubMed]
  • Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000 Nov 30;343(22):1594–1602. [PubMed]
  • Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, Jackson CG, Lange M, Burge DJ. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999 Jan 28;340(4):253–259. [PubMed]
  • Weinblatt Michael E, Keystone Edward C, Furst Daniel E, Moreland Larry W, Weisman Michael H, Birbara Charles A, Teoh Leah A, Fischkoff Steven A, Chartash Elliot K. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003 Jan;48(1):35–45. [PubMed]
  • Furst DE, Breedveld FC, Kalden JR, Smolen JS, Antoni CE, Bijlsma JWJ, Burmester GR, Cronstein B, Keystone EC, Kavanaugh A, et al. Updated consensus statement on biological agents for the treatment of rheumatoid arthritis and other rheumatic diseases (May 2002). Ann Rheum Dis. 2002 Nov;61 (Suppl 2):ii2–ii7. [PMC free article] [PubMed]
  • McAlister FA, Laupacis A, Wells GA, Sackett DL. Users' Guides to the Medical Literature: XIX. Applying clinical trial results B. Guidelines for determining whether a drug is exerting (more than) a class effect. JAMA. 1999 Oct 13;282(14):1371–1377. [PubMed]
  • Fleischmann Roy M. Examining the efficacy of biologic therapy: are there real differences? J Rheumatol Suppl. 2002 Sep;65:27–32. [PubMed]
  • Dayer Jean-Michel, Bresnihan Barry. Targeting interleukin-1 in the treatment of rheumatoid arthritis. Arthritis Rheum. 2002 Mar;46(3):574–578. [PubMed]

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