Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. 2004 May; 63(5): 508–516.
PMCID: PMC1755008

Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed


Objective: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed.

Methods: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was ≥20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI).

Results: After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p⩽0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p⩽0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p⩽0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p⩽0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (–0.29, –0.39, –0.38, –0.49 v –0.07; p⩽0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p⩽0.05).

Conclusion: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.

Full Text

The Full Text of this article is available as a PDF (478K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001 Sep 15;358(9285):903–911. [PubMed]
  • Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum. 2002 Feb;46(2):328–346. [PubMed]
  • Furst DE, Keystone EC, Breedveld FC, Kalden JR, Smolen JS, Antoni CE, Burmester GR, Crofford LJ, Kavanaugh A. Updated consensus statement on tumour necrosis factor blocking agents for the treatment of rheumatoid arthritis and other rheumatic diseases (April 2001). Ann Rheum Dis. 2001 Nov;60 (Suppl 3):iii2–iii5. [PMC free article] [PubMed]
  • Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, Leeb B, Breedveld FC, Macfarlane JD, Bijl H, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 1994 Oct 22;344(8930):1105–1110. [PubMed]
  • Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, Ettlinger RE, Cohen S, Koopman WJ, Mohler K, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med. 1997 Jul 17;337(3):141–147. [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]
  • den Broeder AA, Joosten LAB, Saxne T, Heinegård D, Fenner H, Miltenburg AMM, Frasa WLH, van Tits LJ, Buurman WA, van Riel PLCM, et al. Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. Ann Rheum Dis. 2002 Apr;61(4):311–318. [PMC free article] [PubMed]
  • Weisman Michael H, Moreland Larry W, Furst Daniel E, Weinblatt Michael E, Keystone Edward C, Paulus Harold E, Teoh Leah S, Velagapudi Raja B, Noertersheuser Peter A, Granneman G Richard, et al. Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. Clin Ther. 2003 Jun;25(6):1700–1721. [PubMed]
  • Barrera P, Joosten LA, den Broeder AA, van de Putte LB, van Riel PL, van den Berg WB. Effects of treatment with a fully human anti-tumour necrosis factor alpha monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNFalpha in patients with rheumatoid arthritis. Ann Rheum Dis. 2001 Jul;60(7):660–669. [PMC free article] [PubMed]
  • Barrera P, van der Maas A, van Ede AE, Kiemeney BALM, Laan RFJM, van de Putte LBA, van Riel PLCM. Drug survival, efficacy and toxicity of monotherapy with a fully human anti-tumour necrosis factor-alpha antibody compared with methotrexate in long-standing rheumatoid arthritis. Rheumatology (Oxford) 2002 Apr;41(4):430–439. [PubMed]
  • Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. [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]
  • Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol. 1982 Sep-Oct;9(5):789–793. [PubMed]
  • van Riel PL, van Gestel AM, van de Putte LB. Development and validation of response criteria in rheumatoid arthritis: steps towards an international consensus on prognostic markers. Br J Rheumatol. 1996 Sep;35 (Suppl 2):4–7. [PubMed]
  • van der Heijde DM, van 't Hof MA, van Riel PL, Theunisse LA, Lubberts EW, van Leeuwen MA, van Rijswijk MH, van de Putte LB. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis. 1990 Nov;49(11):916–920. [PMC free article] [PubMed]
  • van der Heijde DM, Jacobs JW. The original "DAS" and the "DAS28" are not interchangeable: comment on the articles by Prevoo et al. Arthritis Rheum. 1998 May;41(5):942–945. [PubMed]
  • Goldsmith CH, Boers M, Bombardier C, Tugwell P. Criteria for clinically important changes in outcomes: development, scoring and evaluation of rheumatoid arthritis patient and trial profiles. OMERACT Committee. J Rheumatol. 1993 Mar;20(3):561–565. [PubMed]
  • Plant MJ, Williams AL, O'Sullivan MM, Lewis PA, Coles EC, Jessop JD. Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis. Arthritis Rheum. 2000 Jul;43(7):1473–1477. [PubMed]
  • Welsing PM, van Gestel AM, Swinkels HL, Kiemeney LA, van Riel PL. The relationship between disease activity, joint destruction, and functional capacity over the course of rheumatoid arthritis. Arthritis Rheum. 2001 Sep;44(9):2009–2017. [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]
  • Sokka Tuulikki, Pincus Theodore. Eligibility of patients in routine care for major clinical trials of anti-tumor necrosis factor alpha agents in rheumatoid arthritis. Arthritis Rheum. 2003 Feb;48(2):313–318. [PubMed]
  • Moreland LW, Schiff MH, Baumgartner SW, Tindall EA, Fleischmann RM, Bulpitt KJ, Weaver AL, Keystone EC, Furst DE, Mease PJ, et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med. 1999 Mar 16;130(6):478–486. [PubMed]
  • van de Putte LBA, Rau R, Breedveld FC, Kalden JR, Malaise MG, van Riel PLCM, Schattenkirchner M, Emery P, Burmester GR, Zeidler H, et al. Efficacy and safety of the fully human anti-tumour necrosis factor alpha monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis: a 12 week, phase II study. Ann Rheum Dis. 2003 Dec;62(12):1168–1177. [PMC free article] [PubMed]
  • Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001 Oct 11;345(15):1098–1104. [PubMed]
  • Kroesen S, Widmer AF, Tyndall A, Hasler P. Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy. Rheumatology (Oxford) 2003 May;42(5):617–621. [PubMed]

Figures and Tables

Figure 1
Patient disposition.
Figure 2
Percentages of patients treated with adalimumab or placebo who had at least 20%, 50%, and 70% improvements in ACR response criteria (ACR20, ACR50, ACR70; observed values). Comparison versus placebo (Pearson's χ2 test): *p⩽0.05; †p⩽0.01; ...
Figure 3
Percentages of patients treated with adalimumab or placebo who had improvements in the European League Against Rheumatism (EULAR) response criteria (observed values). Comparison versus placebo (Pearson's χ2 test): *p⩽0.05; †p⩽0.01; ...

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...