Clinical Rheumatology

, Volume 27, Issue 4, pp 491–496 | Cite as

Etanercept in the treatment of rheumatoid arthritis: clinical follow-up over one year by ultrasonography

  • Annamaria Iagnocco
  • Chiara Perella
  • Esperanza Naredo
  • Gary Meenagh
  • Fulvia Ceccarelli
  • Emanuela Tripodo
  • Stefania Basili
  • Guido Valesini
Original Article


We evaluated clinically and sonographically the effects of etanercept therapy in patients with rheumatoid arthritis (RA) over 12 months of treatment. Eighteen patients affected by RA who were non-responders or partial responders to disease modifying therapy were commenced on Etanercept treatment. Before starting therapy (T0) and at 12 months (T1), the following parameters were evaluated: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS) for pain, number of painful and swollen joints, health assessment questionnaire (HAQ) and disease activity score in 28 joints (DAS 28). Musculoskeletal ultrasound (US) was performed in the following joints: second and fifth metacarpophalangeal, third interphalangeal, wrist and knee joints and a semiquantitative score (0–3) calculated and used to indicate the presence of a localised inflammatory process (synovitis, tenosynovitis, bursitis) and/or structural damage (bone erosion and cartilaginous change). An overall score was calculated based on the sum of the single scores to obtain a comprehensive score indicative of the global pathological change. The US global scores significantly reduced between T0 and T1 (p < 0.0001). The following laboratory and clinical parameters also significantly reduced: ESR (p < 0.0001), CRP (p < 0.02), VAS (p < 0.001), number of total swollen joints (p < 0.001), number of total painful joints (p < 0.01), HAQ scores (p < 0.05) and DAS 28 (p < 0.0001). A positive response to treatment with Etanercept was demonstrated both by US examination of several joints and by clinical evaluation of several parameters. US is a useful tool in the monitoring of biologic therapy in RA, assessing both inflammatory and destructive changes.


Etanercept Follow-up Rheumatoid arthritis Ultrasonography 


  1. 1.
    Arnett FC, Keat ACS (1997) Spondyloarthropathies. In: Klippel JH, Dieppe PA (eds) Rheumatology. Mosby, St. Louis, pp 10.1–20.12Google Scholar
  2. 2.
    Macias I, Garcia-Perez S, Ruiz-Tudela M, Medina F, Chozas N, Giron-Gonzalez JA (2005) Modification of pro- and antiinflammatory cytokines and vascular-related molecules by tumor necrosis factor-a blockade in patients with rheumatoid arthritis. J Rheumatol 32:2102–2108PubMedGoogle Scholar
  3. 3.
    Feldmann M, Brennan FM, Foxwell BM, Maini RN (2001) The role of TNF alpha and IL-1 in rheumatoid arthritis. Curr Dir Autoimmun 3:188–199PubMedCrossRefGoogle Scholar
  4. 4.
    Taylor PC, Sivakumar B (2005) Hypoxia and angiogenesis in rheumatoid arthritis. Curr Opin Rheumatol 17:293–298PubMedCrossRefGoogle Scholar
  5. 5.
    Ritchlin CT (2004) Mechanisms of erosion in rheumatoid arthritis. J Rheumatol 31:1229–1237PubMedGoogle Scholar
  6. 6.
    Furst DE, Breedveld FC, Kalden JR, Smolen JS, Antoni CE, Bijlsma JWJ et al (2002) Updated consesus statement on biological agents for the treatment of rheumatoid arthritis and other rheumatic diseases. Ann Rheum Dis 61(Suppl II):ii2–ii7PubMedGoogle Scholar
  7. 7.
    Bresnihan B (2002) Effects of anakinra on clinical and radiological outcomes in rheumatoid arthritis. Ann Rheum Dis 61(Suppl II):ii74–ii77PubMedGoogle Scholar
  8. 8.
    Maini RN, Taylor PC, Paleolog E (1999) Anti-tumor necrosis factor specific antibody (infliximab) treatment provides insights into the pathophysiology of rheumatoid arthritis. Ann Rheum Dis 58(Suppl I):I156–II60Google Scholar
  9. 9.
    Kruithof E, Van den Bosch F, Baeten D, Herssens A, de Keyser F, Mielants H, Veys EM (2002) Repeated infusions of infliximab, a chimeric anti-TNFα monoclonal antibody, in patients with active spondyloarthropathy: one year follow up. Ann Rheum Dis 61:207–212PubMedCrossRefGoogle Scholar
  10. 10.
    Van der Heijde D, Klareskog L, Singh A, Tornero J, Melo-Gomes J, Codreanu C et al (2006) Patient reported outcomes in a trial of combination therapy with etanercept and methotrexate for rheumatoid arthritis: the TEMPO trial. Ann Rheum Dis 65(3):328–334PubMedCrossRefGoogle Scholar
  11. 11.
    Moreland L (2004) Etanercept and methotrexate combination in rheumatoid arthritis. Curr Rheumatol Rep 6(5):333Google Scholar
  12. 12.
    Wakefield RJ, Gibbon WW, Emery P (1999) The current status of ultrasonography in rheumatology. Rheumatology 38:195–198PubMedCrossRefGoogle Scholar
  13. 13.
    Alarcon GS, Lopex-Ben R, Moreland LW (2002) High-resolution ultrasound for the study of target joints in rheumatoid arthritis. Arthritis Rheum 46:1969–1980PubMedCrossRefGoogle Scholar
  14. 14.
    Newman JS, Laing TJ, McCarthy CJ, Adler RS (1996) Power Dopppler sonography of synovitis: assessment of therapeutic response-preliminary observations. Radiology 198:582–584PubMedGoogle Scholar
  15. 15.
    Walther M, Harms H, Krenn V, Radke S, Faehndrich TP, Gohlke F (2001) Correlation of power Doppler sonography with vascularity of the synovial tissue of the knee joint in patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum 44:331–338PubMedCrossRefGoogle Scholar
  16. 16.
    Wakefield RJ, Gibbon WW, Conaghan PG, O’Connor P, McGonagle D, Pease C et al (2000) The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography. Arthritis Rheum 43:2762–2770PubMedCrossRefGoogle Scholar
  17. 17.
    Backhaus M, Burmester G-R, Gerber T, Grassi W, Machold KP, Swen WA et al (2001) Guidelines for musculoskeletal ultrasound in rheumatology. Ann Rheum Dis 60:641–649PubMedCrossRefGoogle Scholar
  18. 18.
    Schmidt WA, Schmidt H, Schicke B, Gromnica-Ihle E (2004) Standard reference values for musculoskeletal ultrasonography. Ann Rheum Dis 63(8):988–994PubMedCrossRefGoogle Scholar
  19. 19.
    Balint PV, Kane D, Wilson H (2002) Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy. Ann Rheum Dis 61:905–910PubMedCrossRefGoogle Scholar
  20. 20.
    Frediani B, Falsetti P, Storri L, Allegri A, Bisogno S, Baldi F et al (2002) Ultrasound and clinical evaluation of quadricipital tendon enthesitis in patients with psoriatic arthritis and rheumatoid arthritis. Clin Rheumatol 21:203–206PubMedCrossRefGoogle Scholar
  21. 21.
    Naranjo A, Marrero-Pulido T, Ojeda S, Francisco F, Erausquin C, Rua-Figueroa I et al (2002) Abnormal sonographic findings in the asymptomatic arthritic shoulder. Scand J Rheumatol 31(1):17–21PubMedCrossRefGoogle Scholar
  22. 22.
    Wakefield RJ, Balint PV, Szkudlarek M, Filippucci E, Backhaus M, D’Agostino MA et al OMERACT 7 Special Interest Group (2005) Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol 32(12):2485–2487PubMedGoogle Scholar
  23. 23.
    Iagnocco A, Ossandon A, Coari G, Conti F, Priori R, Alessandri C et al (2004) Wrist joint involvement in systemic lupus erythematosus. An ultrasonographic study. Clin Exp Rheumatol 22(5):621–624PubMedGoogle Scholar
  24. 24.
    Szkudlarek M, Court-Payen M, Strandberg C, Klarlund M, Klausen T, Østergaard M (2001) Power doppler ultrasonography for assessment of synovitis in the metacarpophalangeal joints of patients with rheumatoid arthritis. Arthritis Rheum 44(9):2018–2023PubMedCrossRefGoogle Scholar
  25. 25.
    D’Agostino MA, Breban M, Said-Nahal R, Dougados M (2002) Refractory inflammatory heel pain in spondylarthropathy: a significant response to infliximab documented by ultrasound. Arthritis Rheum 46(3):840–841PubMedCrossRefGoogle Scholar
  26. 26.
    Ribbens C, Andre B, Marcelis S, Kaye O, Mathy L, Bonnet V et al (2003) Rheumatoid hand joint synovitis: gray-scale and power Doppler US quantifications following anti-tumor necrosis factor-alpha treatment: pilot study. Radiology 229(2):562–569PubMedCrossRefGoogle Scholar
  27. 27.
    Taylor PC, Steuer A, Gruber J, McClinton C, Cosgrove DO, Blomley MJ et al (2005) Ultrasonographic and radiographic results from a two-year controlled trial of immediate or one-year-delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis. Arthritis Rheum 54(1):47–53CrossRefGoogle Scholar
  28. 28.
    Hau M, Kneitz C, Tony HP, Keberle M, Jahans R, Jenett M (2002) High resolution ultrasound detects a decrease in pannus vascularisation of small finger joints in patients with rheumatoid arthritis. Ann Rheum Dis 61:55–58PubMedCrossRefGoogle Scholar
  29. 29.
    Terslev L, Torp-Pedersen S, Qvistgaard E, Kristoffersen H, Rogind H, Danneskiold-Samsoe B et al (2003) Effects of treatment with etanercept (Enbrel, TNRF:Fc) on rheumatoid arthritis evaluated by Doppler ultrasonography. Ann Rheum Dis 62:178–181PubMedCrossRefGoogle Scholar
  30. 30.
    Fiocco U, Ferro F, Vezzu M, Cozzi L, Checchetto C, Sfriso P et al (2005) Rheumatoid and psoriatic knee synovitis: clinical, grey scale, and power Doppler ultrasound assessment of the response to etanercept. Ann Rheum Dis 64(6):899–905PubMedCrossRefGoogle Scholar
  31. 31.
    Cardinal E, Lafortune M, Burns P (1996) Power Doppler us in synovitis: reality or artifact? Radiology 200(3):868–869PubMedGoogle Scholar
  32. 32.
    Klauser A, Frauscher F, Schirmer M, Halpern E, Pallwein L, Herold M et al (2002) The value of contrast-enhanced color Doppler ultrasound in the detection of vascularization of finger joints in patients with rheumatoid arthritis. Arthritis Rheum 46(3):647–653PubMedCrossRefGoogle Scholar
  33. 33.
    Klocke R, Glew D, Cox N, Blake DR (2001) Sonographic erosions of the rheumatoid little toe. Ann Rheum Dis 60:896–904PubMedGoogle Scholar
  34. 34.
    Magarelli N, Guglielmi G, Di Matteo L, Tartaro A, Mattei PA, Bonomo L (2001) Diagnostic utility of an echo-contrast agent in patients with synovitis using power Doppler ultrasound: a preliminary study with comparison to contrast-enhanced MRI. Eur Radiol 11:1039–1046PubMedCrossRefGoogle Scholar
  35. 35.
    Stone M, Bergin D, Whelan B, Maher M, Murray J, McCarthy C (2001) Power Doppler ultrasound assessment of rheumatoid hand synovitis. J Rheumatol 28(9):1979–1982PubMedGoogle Scholar
  36. 36.
    St Clair EW (2002) Infliximab treatment for rheumatic disease: clinical and radiological efficacy. Ann Rheum Dis 61(Suppl II):ii67–ii69PubMedGoogle Scholar
  37. 37.
    Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Biurbara CA et al (2003) Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 48:35–45PubMedCrossRefGoogle Scholar
  38. 38.
    Antoni C, Dechant C, Hanns-Martin Lorenz PD, Wendler J, Ogilvie A, Lueftl M et al (2002) Open-label study of infliximab treatment for psoriatic arthritis: clinical and magnetic resonance imaging measurements of reduction of inflammation. Arthritis Rheum 47(5):506–512PubMedCrossRefGoogle Scholar
  39. 39.
    Braun J, Sieper J, Breban M, Collantes-Estevez E, Davis J, Inman R et al (2002) Anti-tumor necrosis factor α therapy for ankylosing spondylitis: international experience. Ann Rheum Dis 61(Suppl III):iii51–iii60PubMedGoogle Scholar
  40. 40.
    Charles PJ, Smeenk RTJ, De Jong J, Feldmann M, Maini RN (2000) Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor α. Arthritis Rheum 43(11):2383–2390PubMedCrossRefGoogle Scholar
  41. 41.
    Garrison L, McDonnell ND (1999) Etanercept: therapeutic use in patients with rheumatoid arthritis. Ann Rheum Dis 58(suppl I):I65–I69PubMedCrossRefGoogle Scholar
  42. 42.
    Jones G, Halbert J, Crotty M, Shanahan EM, Batterham M, Ahern M (2003) The effect of treatment on radiological progression in rheumatoid arthritis: a systematic review of randomized placebo-controlled trials. Rheumatology 42:6–13PubMedCrossRefGoogle Scholar
  43. 43.
    Rau R (2002) Adalimumab (a fully human anti-tumor necrosis factor α monoclonal antibody) in the treatment of active rheumatoid arthritis: the initial results of five trials. Ann Rheum Dis 61(Suppl II):ii70–ii73PubMedGoogle Scholar
  44. 44.
    Sokka T, Pincus T (2003) Elegibility of patients in routine care for major clinical trials of anti-tumor necrosis factor α agents in rheumatoid arthritis. Arthritis Rheum 48:313–318PubMedCrossRefGoogle Scholar
  45. 45.
    St Clair EW, Wagner CL, Fasanmade AA, Wang B, Schaible T, Kavanaugh A et al (2002) The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis. Arthritis Rheum 46:1451–1459PubMedCrossRefGoogle Scholar
  46. 46.
    Ulfgren AK, Andersson U, Engstromm M, Klareskog L, Maini RN, Taylor PC (2000) Systemic anti-tumor necrosis factor α therapy in rheumatoid arthritis down-regulates synovial tumor necrosis α synthesis. Arthritis Rheum 43:2391–2396PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2007

Authors and Affiliations

  • Annamaria Iagnocco
    • 1
    • 4
  • Chiara Perella
    • 1
  • Esperanza Naredo
    • 2
  • Gary Meenagh
    • 3
  • Fulvia Ceccarelli
    • 1
  • Emanuela Tripodo
    • 1
  • Stefania Basili
    • 1
  • Guido Valesini
    • 1
  1. 1.Rheumatology UnitUniversity of Rome “La Sapienza”RomeItaly
  2. 2.Department of RheumatologySevero Ochoa HospitalMadridSpain
  3. 3.Department of RheumatologyMusgrave Park HospitalBelfastUK
  4. 4.Dipartimento Clinica e Terapia Medica, Cattedra di Reumatologia“Sapienza” Università di RomaRomeItaly

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