Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed
van de Putte, B. A.; Atkins, C.; Malaise, Michelet al.
2004 • In Annals of the Rheumatic Diseases, 63 (5), p. 508-516
[en] 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 greater than or equal to 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%; pless than or equal to 0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; pless than or equal to 0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; pless than or equal to 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%; pless than or equal to 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; pless than or equal to 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 (pless than or equal to 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.
Disciplines :
Rheumatology
Author, co-author :
van de Putte, B. A.
Atkins, C.
Malaise, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Rhumatologie
Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed
Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet 2001;358:903-11.
American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum 2002;46:328-46.
Furst DE, Keystone EC, Breedveld FC, Kalden JR, Smolen JS, Antoni CE, et al. 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;60(suppl III):iii2-5.
Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, 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;344:1105-10.
Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997;337:141-7.
Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbora CA, et al. 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;48:35-45.
Salfeld J, Kaymakçalan Z, Tracey D, Roberts A, Kamen R. Generation of fully human anti-TNF antibody D2E7 [abstract]. Arthritis Rheum 1998;41(suppl 9):S57.
den Broeder AA, Joosten LA, Saxne T, Heinegard D, Fenner H, Miltenburg AM, 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;61:311-18.
Weisman MH, Moreland LW, Furst DE, Weinblatt ME, Keystone EC, Paulus HE, 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;25:1700-21.
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 α monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNF α in patients with rheumatoid arthritis. Ann Rheum Dis 2001;60:660-9.
Barrera P, van der Maas A, van Ede AE, Kiemeney BA, Laan RF, van de Putte LB, et al. Drug survival, efficacy and toxicity or monotherapy with a fully human anti-tumour necrosis factor-alpha antibody compared with methotrexate in long-standing rheumatoid arthritis. Rheumatology (Oxford) 2002;41:430-9.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.
Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum 1993;36:729-40.
Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the Health Assessment Questionnaire, disability and pain scales. J Rheumatol 1982;9:789-93.
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;35(suppl 2):4-7.
van Gestel AM, Prevoo MLL, van't Hof MA, van Rijswijk MH, van de Putte LBA, van Riel PLCM. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum 1996;39:34-40.
van Riel PLCM, van Gestel AM, Scott DL, on behalf of the EULAR Standing Committee for International Clinical Studies Including Therapeutic Trials. The EULAR handbook of clinical assessments in rheumatoid arthritis. Alpen an den Rijn. The Netherlands: Van Zuiden Communications, 2000.
Prevoo MLL, van't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LBA, van Riel PLCM. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44-8.
van der Heijde DMFM, van't Hof MA, van Riel PLCM, Theunisse LAM, Lubberts EW, van Leeuwen MA, et al. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis 1990;49:916-20.
van der Heijde DMFM, Jacobs JWG. The original "DAS" and the "DAS28" are not interchangeable: comment on the articles by Prevoo et al [letter]. Arthritis Rheum 1998;41:942-3.
Humira™ (adalimumab) [package insert]. North Chicago, IL: Abbott Laboratories, 2004.
Goldsmith CH, Boers M, Bombardier C, Tugwell P, for the OMERACT Committee. Criteria for clinically important changes in outcomes: development, scoring and evaluation of rheumatoid arthritis patient and trial profiles. J Rheumatol 1993;20:561-5.
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;43:1473-7.
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;44:2009-17.
Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, et al. Infliximab (chimeric anti-tumour necrosis factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet 1999;354:1932-9.
Sokka T, Pincus T. Eligibility of patients in routine care for major clinical trials of anti-tumor necrosis factor α agents in rheumatoid arthritis. Arthritis Rheum 2003;48:313-18.
Moreland LW, Schiff MH, Baumgartner SW, Tindall EA, Fleischmann RM, Bulpitt KJ, et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med 1999;130:478-86.
van da Putte LBA, Rau R, Breedveld FC, Kalden JR, Malaise MA, Schattenkirchner M, et al. Efficacy and safety of the fully human anti-TNF-α monoclonal antibody, adalimumab (D2E7), in DMARD-refractory patients with rheumatoid arthritis: a 12-week, phase II study. Ann Rheum Dis 2003;62:1168-77.
Wells AF, Kupper H, Fischkoff S, Chartash E. Incidence of injection-site reactions associated with adalimumab (D2E7) given subcutaneously for at leost 6 months: a retrospective analysis of 4 phase II/III clinical trials [abstract]. Arthritis Rheum 2002;46(uppl 9):S171.
Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001;345:1098-104.
Kroesen S, Widmer AF, Tyndall A, Hasler P. Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy. Rheumatology (Oxford) 2003;42:617-21.
