Skip to main content

Advertisement

SpringerLink
Log in

Meta-analysis of the combination of TNF inhibitors plus MTX compared to MTX monotherapy, and the adjusted indirect comparison of TNF inhibitors in patients suffering from active rheumatoid arthritis

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

This present study was designed to examine (1) whether a combination therapy of TNF (tumor necrosis factor) blockers and methotrexate (MTX) is better than MTX monotherapy, and (2) if the TNF inhibitors such as etanercept, infliximab and adalimumab are all same for treating patients with active rheumatoid arthritis (RA). We performed meta-analysis of a combination therapy of TNF-blockers and MTX compared to MTX monotherapy and we performed adjusted indirect comparison of the TNF-blocking agents for their efficacy and toxicity. Three studies met the inclusion criteria for the analysis. Meta-analysis showed that the combination of MTX with anti-TNF inhibitors was more effective than MTX monotherapy and this indicated that combination therapy of anti-TNF inhibitors and MTX was comparable with MTX monotherapy in terms of withdrawal due to the side effects (RR: 1.05, 95% CI: 0.52–2.09, P = 0.86). The adjusted indirect comparison did not show any differences between infliximab and adalimumab. However, there was a significant difference for clinical efficacy and side effects between etanercept, adalimumab and infliximab. The RRs for achieving ACR20, ACR50 and ACR70 responses and withdrawal due to the side effect in the etanercept group were lower when compared with the adalimumab group. The RR for achieving an ACR20 response in the etanercept group was lower when compared with the infliximab group. The adjusted indirect comparison analysis suggests that the TNF-blocking agents all are not the same with respect to effectiveness and toxicity for the treatment of active RA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Reference

  1. Choy EH, Panayi GS (2001) Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 344:907–916

    Article  PubMed  CAS  Google Scholar 

  2. Mohler KM, Torrance DS, Smith CA, Goodwin RG, Stremler KE, Fung VP, Madani H, Widmer MB (1993) Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 151:1548–1561

    PubMed  CAS  Google Scholar 

  3. Scallon BJ, Moore MA, Trinh H, Knight DM, Ghrayeb J (1995) Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine 7:251–259

    Article  PubMed  CAS  Google Scholar 

  4. Mpofu S, Fatima F, Moots RJ (2005) Anti-TNF-alpha therapies: they are all the same (aren’t they?). Rheumatology (Oxford) 44:271–273

    Article  Google Scholar 

  5. Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Bijlsma JW, Dougados M, Emery P, Keystone EC, Klareskog L, Mease PJ (2005) Updated consensus statement on biological agents, specifically tumour necrosis factor {alpha} (TNF{alpha}) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases, 2005. Ann Rheum Dis 649(Suppl 4):iv2–iv14

    Article  Google Scholar 

  6. Klareskog L, van der HD, de Jager JP, Gough A, Kalden J, Malaise M, Martin ME, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M (2004) Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363:675–681

    Article  PubMed  CAS  Google Scholar 

  7. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN (2000) 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 343:1594–1602

    Article  PubMed  CAS  Google Scholar 

  8. Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, Fischkoff SA, Chartash EK (2004) Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 50:1400–1411

    Article  PubMed  CAS  Google Scholar 

  9. Song F, Altman DG, Glenny AM, Deeks JJ (2003) Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 326:472

    Article  PubMed  Google Scholar 

  10. Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219

    Article  PubMed  Google Scholar 

  11. Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50:683–691

    Article  PubMed  CAS  Google Scholar 

  12. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12

    Article  PubMed  CAS  Google Scholar 

  13. Davey SG, Egger M (1997) Meta-analyses of randomised controlled trials. Lancet 350:1182

    Google Scholar 

  14. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  15. Hochberg MC, Lebwohl MG, Plevy SE, Hobbs KF, Yocum DE (2005) The benefit/risk profile of TNF-blocking agents: findings of a consensus panel. Semin Arthritis Rheum 34:819–836

    Article  PubMed  CAS  Google Scholar 

  16. Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, DeWoody KL, Schaible TF, Rutgeerts PJ (1997) A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med 337:1029–1035

    Article  PubMed  CAS  Google Scholar 

  17. Sandborn WJ, Hanauer SB, Katz S, Safdi M, Wolf DG, Baerg RD, Tremaine WJ, Johnson T, Diehl NN, Zinsmeister AR (2001) Etanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology 121:1088–1094

    Article  PubMed  CAS  Google Scholar 

  18. Buch MH, Conaghan PG, Quinn MA, Bingham SJ, Veale D, Emery P (2004) True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin alpha? Ann Rheum Dis 63:1344–1346

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Medical Center, 126-1 Ka, Anam-Dong, Seongbuk-Ku, Seoul, 136-705, South Korea

    Young Ho Lee, Jin Hyun Woo, Young Hee Rho, Seong Jae Choi, Jong Dae Ji & Gwan Gyu Song

Authors
  1. Young Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin Hyun Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Young Hee Rho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seong Jae Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jong Dae Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gwan Gyu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Ho Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, Y.H., Woo, J.H., Rho, Y.H. et al. Meta-analysis of the combination of TNF inhibitors plus MTX compared to MTX monotherapy, and the adjusted indirect comparison of TNF inhibitors in patients suffering from active rheumatoid arthritis. Rheumatol Int 28, 553–559 (2008). https://doi.org/10.1007/s00296-007-0475-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-007-0475-6

Keywords

Search

Navigation