European Radiology

, Volume 19, Issue 9, pp 2217–2224 | Cite as

Longitudinal changes in rheumatoid arthritis after rituximab administration assessed by quantitative and dynamic contrast-enhanced 3-T MR imaging: preliminary findings

  • Jan FritzEmail author
  • Eva K. Galeczko
  • Nina Schwenzer
  • Michael Fenchel
  • Claus D. Claussen
  • John A. Carrino
  • Marius S. Horger


We retrospectively assessed the longitudinal changes of rheumatoid arthritis under rituximab therapy by use of quantitative and dynamic contrast-enhanced 3-T magnetic resonance (MR) imaging of the metacarpophalangeal joints of 10 patients at baseline and 26 weeks (n = 10). Additional studies were available at 12 weeks (n = 9) and at 52 weeks (n = 5). Clinical activity was assessed by use of the 28-joint disease activity score (DAS28). MR imaging was used to assess volumes of synovial enhancement, osseous enhancement, and erosions and early rapid enhancement. DAS28 and serum C-reactive protein trended down over time and were significantly lower at 26 weeks. Volume of synovial enhancement and early rapid enhancement showed a significant minimum at 26 weeks and increased thereafter. The erythrocyte sedimentation rate paralleled these two trends. Osseous enhancement did not significantly change over time. Erosions showed a significant progression. Trends of DAS28 and erosions were significantly different (P = 0.0075). In conclusion, our preliminary results suggest that rituximab is associated with a decrease of the inflammatory activity of synovitis with a minimum at 26 weeks and increasing activity thereafter suggesting recurrence. Our results further suggest subclinical progression of erosions with an inverse relationship to decreasing disease activity scores. Further studies are needed to confirm these results.


Rituximab Rheumatoid arthritis Magnetic resonance imaging High-field MR imaging Dynamic contrast-enhanced MR imaging 


  1. 1.
    McLaughlin P, Grillo-Lopez AJ, Link BK et al (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16:2825–2833PubMedGoogle Scholar
  2. 2.
    Edwards JC, Szczepanski L, Szechinski J et al (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350:2572–2581PubMedCrossRefGoogle Scholar
  3. 3.
    Cohen SB, Emery P, Greenwald MW et al (2006) Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 54:2793–2806PubMedCrossRefGoogle Scholar
  4. 4.
    McQueen FM, Benton N, Perry D et al (2003) Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritis. Arthritis Rheum 48:1814–1827PubMedCrossRefGoogle Scholar
  5. 5.
    Ostergaard M, Duer A, Nielsen H et al (2005) Magnetic resonance imaging for accelerated assessment of drug effect and prediction of subsequent radiographic progression in rheumatoid arthritis: a study of patients receiving combined anakinra and methotrexate treatment. Ann Rheum Dis 64:1503–1506PubMedCrossRefGoogle Scholar
  6. 6.
    Palosaari K, Vuotila J, Takalo R et al (2006) Bone oedema predicts erosive progression on wrist MRI in early RA—a 2-yr observational MRI and NC scintigraphy study. Rheumatology (Oxford) 45:1542–1548CrossRefGoogle Scholar
  7. 7.
    McQueen FM (2000) Magnetic resonance imaging in early inflammatory arthritis: what is its role? Rheumatology (Oxford) 39:700–706CrossRefGoogle Scholar
  8. 8.
    Bird P, Lassere M, Shnier R et al (2003) Computerized measurement of magnetic resonance imaging erosion volumes in patients with rheumatoid arthritis: a comparison with existing magnetic resonance imaging scoring systems and standard clinical outcome measures. Arthritis Rheum 48:614–624PubMedCrossRefGoogle Scholar
  9. 9.
    Ostergaard M (1997) Different approaches to synovial membrane volume determination by magnetic resonance imaging: manual versus automated segmentation. Br J Rheumatol 36:1166–1177PubMedCrossRefGoogle Scholar
  10. 10.
    Tam LS, Griffith JF, Yu AB et al (2007) Rapid improvement in rheumatoid arthritis patients on combination of methotrexate and infliximab: clinical and magnetic resonance imaging evaluation. Clin Rheumatol 26:941–946PubMedCrossRefGoogle Scholar
  11. 11.
    Konig H, Sieper J, Wolf KJ (1990) Rheumatoid arthritis: evaluation of hypervascular and fibrous pannus with dynamic MR imaging enhanced with Gd-DTPA. Radiology 176:473–477PubMedGoogle Scholar
  12. 12.
    Ostergaard M, Stoltenberg M, Lovgreen-Nielsen P et al (1998) Quantification of synovistis by MRI: correlation between dynamic and static gadolinium-enhanced magnetic resonance imaging and microscopic and macroscopic signs of synovial inflammation. Magn Reson Imaging 16:743–754PubMedCrossRefGoogle Scholar
  13. 13.
    Huang J, Stewart N, Crabbe J et al (2000) A 1-year follow-up study of dynamic magnetic resonance imaging in early rheumatoid arthritis reveals synovitis to be increased in shared epitope-positive patients and predictive of erosions at 1 year. Rheumatology (Oxford) 39:407–416CrossRefGoogle Scholar
  14. 14.
    Hodgson R, Grainger A, O’Connor P et al (2008) Dynamic contrast enhanced MRI of bone marrow oedema in rheumatoid arthritis. Ann Rheum Dis 67:270–272PubMedCrossRefGoogle Scholar
  15. 15.
    Polisson RP, Schoenberg OI, Fischman A et al (1995) Use of magnetic resonance imaging and positron emission tomography in the assessment of synovial volume and glucose metabolism in patients with rheumatoid arthritis. Arthritis Rheum 38:819–825PubMedCrossRefGoogle Scholar
  16. 16.
    Kalden-Nemeth D, Grebmeier J, Antoni C et al (1997) NMR monitoring of rheumatoid arthritis patients receiving anti-TNF-alpha monoclonal antibody therapy. Rheumatol Int 16:249–255PubMedCrossRefGoogle Scholar
  17. 17.
    Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRefGoogle Scholar
  18. 18.
    van der Heijde DM, van’t Hof MA, van Riel PL et al (1990) Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis 49:916–920PubMedCrossRefGoogle Scholar
  19. 19.
    van Gestel AM, Haagsma CJ, van Riel PL (1998) Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 41:1845–1850PubMedCrossRefGoogle Scholar
  20. 20.
    Tamai K, Yamato M, Yamaguchi T et al (1994) Dynamic magnetic resonance imaging for the evaluation of synovitis in patients with rheumatoid arthritis. Arthritis Rheum 37:1151–1157PubMedCrossRefGoogle Scholar
  21. 21.
    Sonnad SS (2002) Describing data: statistical and graphical methods. Radiology 225:622–628PubMedCrossRefGoogle Scholar
  22. 22.
    Bland JM, Altman DG (1996) Measurement error proportional to the mean. BMJ 313:106PubMedGoogle Scholar
  23. 23.
    Applegate KE, Tello R, Ying J (2003) Hypothesis testing III: counts and medians. Radiology 228:603–608PubMedCrossRefGoogle Scholar
  24. 24.
    Bland M (2000) An introduction to medical statistics. Oxford University Press, OxfordGoogle Scholar
  25. 25.
    Strand V, Balbir-Gurman A, Pavelka K et al (2006) Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements in physical function over 2 years. Rheumatology (Oxford) 45:1505–1513CrossRefGoogle Scholar
  26. 26.
    McGonagle D, Tan AL, Madden J et al (2008) Rituximab use in everyday clinical practice as a first-line biologic therapy for the treatment of DMARD-resistant rheumatoid arthritis. Rheumatology (Oxford) 47:865–867CrossRefGoogle Scholar
  27. 27.
    Argyropoulou MI, Glatzouni A, Voulgari PV et al (2005) Magnetic resonance imaging quantification of hand synovitis in patients with rheumatoid arthritis treated with infliximab. Joint Bone Spine 72:557–561PubMedCrossRefGoogle Scholar
  28. 28.
    Palmer WE, Rosenthal DI, Schoenberg OI et al (1995) Quantification of inflammation in the wrist with gadolinium-enhanced MR imaging and PET with 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 196:647–655PubMedGoogle Scholar
  29. 29.
    Ostergaard M, Stoltenberg M, Lovgreen-Nielsen P et al (1997) Magnetic resonance imaging-determined synovial membrane and joint effusion volumes in rheumatoid arthritis and osteoarthritis: comparison with the macroscopic and microscopic appearance of the synovium. Arthritis Rheum 40:1856–1867PubMedCrossRefGoogle Scholar
  30. 30.
    Ostergaard M, Hansen M, Stoltenberg M et al (1999) Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis. Arthritis Rheum 42:918–929PubMedCrossRefGoogle Scholar
  31. 31.
    Jimenez-Boj E, Nobauer-Huhmann I, Hanslik-Schnabel B et al (2007) Bone erosions and bone marrow edema as defined by magnetic resonance imaging reflect true bone marrow inflammation in rheumatoid arthritis. Arthritis Rheum 56:1118–1124PubMedCrossRefGoogle Scholar
  32. 32.
    Haavardsholm EA, Boyesen P, Ostergaard M et al (2008) Magnetic resonance imaging findings in 84 patients with early rheumatoid arthritis: bone marrow oedema predicts erosive progression. Ann Rheum Dis 67:794–800PubMedCrossRefGoogle Scholar
  33. 33.
    Savnik A, Malmskov H, Thomsen HS et al (2002) MRI of the wrist and finger joints in inflammatory joint diseases at 1-year interval: MRI features to predict bone erosions. Eur Radiol 12:1203–1210PubMedCrossRefGoogle Scholar
  34. 34.
    McQueen FM, Stewart N, Crabbe J et al (1999) Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals progression of erosions despite clinical improvement. Ann Rheum Dis 58:156–163PubMedCrossRefGoogle Scholar
  35. 35.
    Brown AK, Conaghan PG, Karim Z et al (2008) An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. Arthritis Rheum 58:2958–2967PubMedCrossRefGoogle Scholar
  36. 36.
    Molenaar ET, Voskuyl AE, Dinant HJ et al (2004) Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum 50:36–42PubMedCrossRefGoogle Scholar
  37. 37.
    Mulherin D, Fitzgerald O, Bresnihan B (1996) Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ. Br J Rheumatol 35:1263–1268PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2009

Authors and Affiliations

  • Jan Fritz
    • 1
    • 2
    Email author
  • Eva K. Galeczko
    • 1
  • Nina Schwenzer
    • 1
  • Michael Fenchel
    • 1
  • Claus D. Claussen
    • 1
  • John A. Carrino
    • 2
  • Marius S. Horger
    • 1
  1. 1.Department of Diagnostic and Interventional RadiologyEberhard Karls UniversityTübingenGermany
  2. 2.Russell H. Morgan Department of Radiology and Radiological ScienceJohns Hopkins University School of MedicineBaltimoreUSA

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