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Ann Rheum Dis. 2004 Feb; 63(2): 149–155.
PMCID: PMC1754899

Infliximab in active early rheumatoid arthritis


Objective: To examine the impact of the combination of infliximab plus methotrexate (MTX) on the progression of structural damage in patients with early rheumatoid arthritis (RA).

Methods: Subanalyses were carried out on data for patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy (ATTRACT) study, in which 428 patients with active RA despite MTX therapy received placebo with MTX (MTX-only) or infliximab 3 mg/kg or 10 mg/kg every (q) 4 or 8 weeks with MTX (infliximab plus MTX) for 102 weeks. Early RA was defined as disease duration of 3 years or less; 82 of the 428 patients (19%) met this definition. Structural damage was assessed with the modified van der Heijde-Sharp score. The changes from baseline to week 102 in total modified van der Heijde-Sharp score were compared between the infliximab plus MTX groups and the MTX-only group.

Results: The erosion and joint space narrowing scores from baseline to week 102 in the cohort of patients with early RA decreased significantly in each infliximab dose regimen compared with the MTX-only regimen. Consistent benefit was seen in the joints of both hands and feet.

Conclusions: Infliximab combined with MTX inhibited the progression of structural damage in patients with early RA during the 2 year period of treatment. Early intervention with infliximab in patients with active RA despite MTX therapy may provide long term benefits by preventing radiographic progression and preserving joint integrity.

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Selected References

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  • Potter T, Mulherin D, Pugh M. Early intervention with disease-modifying therapy for rheumatoid arthritis: where do the delays occur? Rheumatology (Oxford) 2002 Aug;41(8):953–955. [PubMed]
  • Loughlin J, Dowling B, Mustafa Z, Southam L, Chapman K. Refined linkage mapping of a hip osteoarthritis susceptibility locus on chromosome 2q. Rheumatology (Oxford) 2002 Aug;41(8):955–956. [PubMed]
  • Moreland LW, Bridges SL., Jr Early rheumatoid arthritis: a medical emergency? Am J Med. 2001 Oct 15;111(6):498–500. [PubMed]
  • Aletaha D, Eberl G, Nell VPK, Machold KP, Smolen JS. Practical progress in realisation of early diagnosis and treatment of patients with suspected rheumatoid arthritis: results from two matched questionnaires within three years. Ann Rheum Dis. 2002 Jul;61(7):630–634. [PMC free article] [PubMed]
  • Irvine S, Munro R, Porter D. Early referral, diagnosis, and treatment of rheumatoid arthritis: evidence for changing medical practice. Ann Rheum Dis. 1999 Aug;58(8):510–513. [PMC free article] [PubMed]
  • Emery P, Breedveld FC, Dougados M, Kalden JR, Schiff MH, Smolen JS. Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis. 2002 Apr;61(4):290–297. [PMC free article] [PubMed]
  • Fuchs HA, Kaye JJ, Callahan LF, Nance EP, Pincus T. Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease. J Rheumatol. 1989 May;16(5):585–591. [PubMed]
  • van Everdingen Amalia A, Jacobs Johannes W G, Siewertsz Van Reesema Dirk R, Bijlsma Johannes W J. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med. 2002 Jan 1;136(1):1–12. [PubMed]
  • Lard LR, Visser H, Speyer I, vander Horst-Bruinsma IE, Zwinderman AH, Breedveld FC, Hazes JM. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med. 2001 Oct 15;111(6):446–451. [PubMed]
  • Backhaus M, Burmester GR, Sandrock D, Loreck D, Hess D, Scholz A, Blind S, Hamm B, Bollow M. Prospective two year follow up study comparing novel and conventional imaging procedures in patients with arthritic finger joints. Ann Rheum Dis. 2002 Oct;61(10):895–904. [PMC free article] [PubMed]
  • McQueen FM, Benton N, Crabbe J, Robinson E, Yeoman S, McLean L, Stewart N. What is the fate of erosions in early rheumatoid arthritis? Tracking individual lesions using x rays and magnetic resonance imaging over the first two years of disease. Ann Rheum Dis. 2001 Sep;60(9):859–868. [PMC free article] [PubMed]
  • Möttönen Timo, Hannonen Pekka, Korpela Markku, Nissilä Martti, Kautiainen Hannu, Ilonen Jorma, Laasonen Leena, Kaipiainen-Seppänen Oili, Franzen Per, Helve Tapani, et al. Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum. 2002 Apr;46(4):894–898. [PubMed]
  • Aletaha D, Smolen JS. The rheumatoid arthritis patient in the clinic: comparing more than 1,300 consecutive DMARD courses. Rheumatology (Oxford) 2002 Dec;41(12):1367–1374. [PubMed]
  • Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum. 2000 Jan;43(1):22–29. [PubMed]
  • Hochberg MC. Early aggressive DMARD therapy: the key to slowing disease progression in rheumatoid arthritis. Scand J Rheumatol Suppl. 1999;112:3–7. [PubMed]
  • Stenger AA, Van Leeuwen MA, Houtman PM, Bruyn GA, Speerstra F, Barendsen BC, Velthuysen E, van Rijswijk MH. Early effective suppression of inflammation in rheumatoid arthritis reduces radiographic progression. Br J Rheumatol. 1998 Nov;37(11):1157–1163. [PubMed]
  • Kvien TK, Zeidler HK, Hannonen P, Wollheim FA, Førre O, Hafström I, Kaltwasser JP, Leirisalo-Repo M, Manger B, Laasonen L, et al. Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension. Ann Rheum Dis. 2002 Jun;61(6):511–516. [PMC free article] [PubMed]
  • Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, van Zeben D, Dijkmans BA, Peeters AJ, Jacobs P, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997 Aug 2;350(9074):309–318. [PubMed]
  • van der Heide A, Jacobs JW, Bijlsma JW, Heurkens AH, van Booma-Frankfort C, van der Veen MJ, Haanen HC, Hofman DM, van Albada-Kuipers GA, ter Borg EJ, et al. The effectiveness of early treatment with "second-line" antirheumatic drugs. A randomized, controlled trial. Ann Intern Med. 1996 Apr 15;124(8):699–707. [PubMed]
  • Calgüneri M, Pay S, Calişkaner Z, Apraş S, Kiraz S, Ertenli I, Cobankara V. Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthritis. Clin Exp Rheumatol. 1999 Nov-Dec;17(6):699–704. [PubMed]
  • Mulherin D, Fitzgerald O, Bresnihan B. Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ. Br J Rheumatol. 1996 Dec;35(12):1263–1268. [PubMed]
  • Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Genovese MC, Wasko MC, Moreland LW, Weaver AL, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000 Nov 30;343(22):1586–1593. [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]
  • van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol. 2000 Jan;27(1):261–263. [PubMed]
  • van der Heijde D, Dankert T, Nieman F, Rau R, Boers M. Reliability and sensitivity to change of a simplification of the Sharp/van der Heijde radiological assessment in rheumatoid arthritis. Rheumatology (Oxford) 1999 Oct;38(10):941–947. [PubMed]
  • Lassere M, Boers M, van der Heijde D, Boonen A, Edmonds J, Saudan A, Verhoeven AC. Smallest detectable difference in radiological progression. J Rheumatol. 1999 Mar;26(3):731–739. [PubMed]
  • van der Heijde Désirée, Simon Lee, Smolen Josef, Strand Vibeke, Sharp John, Boers Maarten, Breedveld Ferdinand, Weisman Michael, Weinblatt Michael, Rau Rolf, et al. How to report radiographic data in randomized clinical trials in rheumatoid arthritis: guidelines from a roundtable discussion. Arthritis Rheum. 2002 Apr 15;47(2):215–218. [PubMed]
  • Hulsmans HM, Jacobs JW, van der Heijde DM, van Albada-Kuipers GA, Schenk Y, Bijlsma JW. The course of radiologic damage during the first six years of rheumatoid arthritis. Arthritis Rheum. 2000 Sep;43(9):1927–1940. [PubMed]
  • Assmann SF, Pocock SJ, Enos LE, Kasten LE. Subgroup analysis and other (mis)uses of baseline data in clinical trials. Lancet. 2000 Mar 25;355(9209):1064–1069. [PubMed]

Figures and Tables

Figure 1
Median change in total radiographic score from baseline to week 102 for all patients with RA (All) v patients with early RA (ERA) who were randomised to MTX only (MTX) or infliximab plus MTX (Infliximab+MTX) in ATTRACT (disease duration ⩽3 years). ...
Figure 2
Median change in erosion scores from baseline to week 102 for patients with early RA in ATTRACT (disease duration ⩽3 years).
Figure 3
Median change in joint space narrowing scores from baseline to week 102 for patients with early RA in ATTRACT (disease duration ⩽3 years).
Figure 4
Proportions of patients with change >SDD and change >0.5 from baseline in modified van der Heijde-Sharp score at week 102. p = 0.069 for 3 mg/kg every 4 weeks v placebo, >0.5 cut off criteria. p<0.05 infliximab v placebo ...

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