Skip to main content

Advertisement

SpringerLink
Log in

Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints and tendons should be assessed to predict unstable remission?

  • Original Article - Imaging
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0–3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist–MCP–ankle–MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist–hand–ankle–MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G et al (2010) Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 69(4):631–637. doi:10.1136/ard.2009.123919

    Article  PubMed Central  PubMed  Google Scholar 

  2. Smolen JS, Landewé R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C et al (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69(6):964–975. doi:10.1136/ard.2009.126532

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J et al (2011) American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 70(3):404–413. doi:10.1136/ard.2011.149765

    Article  PubMed  Google Scholar 

  4. Backhaus M, Burmester GR, Sandrock D, Loreck D, Hess D, Scholz A, Blind S, Hamm B, Bollow M (2001) Prospective two year follow up study comparing novel and conventional imaging procedures in patients with arthritic finger joints. Ann Rheum Dis 61(10):895–904

    Article  Google Scholar 

  5. Wakefield RJ, Green MJ, Marzo-Ortega H, Conaghan PG, Gibbon WW, McGonagle D, Proudman S, Emery P (2004) Should oligoarthritis be reclassified? Ultrasound reveals a high prevalence of subclinical disease. Ann Rheum Dis 63(4):382–385

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Naredo E, Bonilla G, Gamero F, Uson J, Carmona L, Laffon A (2005) Assessment of inflammatory activity in rheumatoid arthritis: a comparative study of clinical evaluation with grey scale and power Doppler ultrasonography. Ann Rheum Dis 64(3):375–381

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Filippucci E, Gabba A, Di Geso L, Girolimetti R, Salaffi F, Grassi W (2012) Hand tendon involvement in rheumatoid arthritis: an ultrasound study. Semin Arthritis Rheum 41(6):752–760. doi:10.1016/j.semarthrit.2011.09.006

    Article  PubMed  Google Scholar 

  8. 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(2):331–338

    Article  CAS  PubMed  Google Scholar 

  9. Szkudlarek M, Court-Payen M, Strandberg C, Klarlund M, Klausen T, Ostergaard M (2001) Power Doppler ultrasonography for assessment of synovitis in the metacarpophalangeal joints of patients with rheumatoid arthritis: a comparison with dynamic magnetic resonance imaging. Arthritis Rheum 44(9):2018–2023

    Article  CAS  PubMed  Google Scholar 

  10. Terslev L, Torp-Pedersen S, Savnik A, von der Recke P, Qvistgaard E, Danneskiold-Samsøe B, Bliddal H (2003) Doppler ultrasound and magnetic resonance imaging of synovial inflammation of the hand in rheumatoid arthritis: a comparative study. Arthritis Rheum 48(9):2434–2441

    Article  CAS  PubMed  Google Scholar 

  11. Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, Wakefield RJ, O’Connor PJ, Emery P (2006) Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression. Arthritis Rheum 54(12):3761–3773

    Article  CAS  PubMed  Google Scholar 

  12. Wakefield RJ, Freeston JE, Hensor EM, Bryer D, Quinn MA, Emery P (2007) Delay in imaging versus clinical response: a rationale for prolonged treatment with anti-tumor necrosis factor medication in early rheumatoid arthritis. Arthritis Rheum 57(8):1564–1567

    Article  PubMed  Google Scholar 

  13. Brown AK, Conaghan PG, Karim Z, Quinn MA, Ikeda K, Peterfy CG, Hensor E, Wakefield RJ, O’Connor PJ, Emery P (2008) An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. Arthritis Rheum 58(10):2958–2967. doi:10.1002/art.23945

    Article  CAS  PubMed  Google Scholar 

  14. Scirè CA, Montecucco C, Codullo V, Epis O, Todoerti M, Caporali R (2009) Ultrasonographic evaluation of joint involvement in early rheumatoid arthritis in clinical remission: power Doppler signal predicts short-term relapse. Rheumatology 48(9):1092–1097. doi:10.1093/rheumatology/kep171

    Article  PubMed  Google Scholar 

  15. Saleem B, Brown AK, Keen H, Nizam S, Freeston J, Karim Z, Quinn M, Wakefield R, Hensor E, Conaghan PG, Emery P (2009) Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease-modifying antirheumatic drugs: a clinical and imaging comparative study. Arthritis Rheum 60(7):1915–1922. doi:10.1002/art.24596

    Article  CAS  PubMed  Google Scholar 

  16. Balsa A, de Miguel E, Castillo C, Peiteado D, Martín-Mola E (2010) Superiority of SDAI over DAS-28 in assessment of remission in rheumatoid arthritis patients using power Doppler ultrasonography as a gold standard. Rheumatology 49(4):683–690. doi:10.1093/rheumatology/kep442

    Article  PubMed  Google Scholar 

  17. Peluso G, Michelutti A, Bosello S, Gremese E, Tolusso B, Ferraccioli G (2011) Clinical and ultrasonographic remission determines different chances of relapse in early and long standing rheumatoid arthritis. Ann Rheum Dis 70(1):172–175. doi:10.1136/ard.2010.129924

    Article  PubMed  Google Scholar 

  18. Saleem B, Brown AK, Keen H, Nizam S, Freeston J, Wakefield R, Karim Z, Quinn M, Hensor E, Conaghan PG, Emery P (2011) Should imaging be a component of rheumatoid arthritis remission criteria? A comparison between traditional and modified composite remission scores and imaging assessments. Ann Rheum Dis 70(5):792–798. doi:10.1136/ard.2010.134445

    Article  PubMed  Google Scholar 

  19. Saleem B, Brown AK, Quinn M, Karim Z, Hensor EM, Conaghan P, Peterfy C, Wakefield RJ, Emery P (2012) Can flare be predicted in DMARD treated RA patients in remission, and is it important? A cohort study. Ann Rheum Dis 71(8):1316–1321. doi:10.1136/annrheumdis-2011-200548

    Article  PubMed  Google Scholar 

  20. Sakellariou G, Scirè CA, Verstappen SM, Montecucco C, Caporali R (2013) In patients with early rheumatoid arthritis, the new ACR/EULAR definition of remission identifies patients with persistent absence of functional disability and suppression of ultrasonographic synovitis. Ann Rheum Dis 72(2):245–249. doi:10.1136/annrheumdis-2012-201817

    Article  PubMed  Google Scholar 

  21. Yoshimi R, Hama M, Takase K, Ihata A, Kishimoto D, Terauchi K, Watanabe R, Uehara T, Samukawa S, Ueda A, Takeno M, Ishigatsubo Y (2013) Ultrasonography is a potent tool for the prediction of progressive joint destruction during clinical remission of rheumatoid arthritis. Mod Rheumatol 23(3):456–465. doi:10.1007/s10165-012-0690-1

    Article  CAS  PubMed  Google Scholar 

  22. Naredo E, Valor L, De la Torre I, Martínez-Barrio J, Hinojosa M, Aramburu F, Ovalles-Bonilla JG, Hernández D, Montoro M, González CM, López-Longo J, Monteagudo I, Carreño L (2013) Ultrasound joint inflammation in rheumatoid arthritis in clinical remission: How many and which joints should be assessed? Arthritis Care Res 65(4):512–517. doi:10.1002/acr.21869

    Article  Google Scholar 

  23. Foltz V, Gandjbakhch F, Etchepare F, Rosenberg C, Tanguy ML, Rozenberg S, Bourgeois P, Fautrel B (2012) Power Doppler ultrasound, but not low-field magnetic resonance imaging, predicts relapse and radiographic disease progression in rheumatoid arthritis patients with low levels of disease activity. Arthritis Rheum 64(1):67–76. doi:10.1002/art.33312

    Article  PubMed  Google Scholar 

  24. Jain A, Nanchahal J, Troeberg L, Green P, Brennan F (2001) Production of cytokines, vascular endothelial growth factor, matrix metalloproteinases, and tissue inhibitor of metalloproteinases 1 by tenosynovium demonstrates its potential for tendon destruction in rheumatoid arthritis. Arthritis Rheum 44(8):1754–1760

    Article  CAS  PubMed  Google Scholar 

  25. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324

    Article  CAS  PubMed  Google Scholar 

  26. Smolen JS, Breedveld FC, Eberl G, Jones I, Leeming M, Wylie GL, Kirkpatrick J (1995) Validity and reliability of the twenty-eight-joint count for the assessment of rheumatoid arthritis activity. Arthritis Rheum 38(1):38–43

    Article  CAS  PubMed  Google Scholar 

  27. Esteve-Vives J, Batlle-Gualda E, Reig A (1993) Spanish version of the Health Assessment Questionnaire: reliability, validity and transcultural equivalency. J Rheumatol 20:2116–2122

    CAS  PubMed  Google Scholar 

  28. Wakefield RJ, Balint PV, Szkudlarek M, Filippucci E, Backhaus M, D’Agostino MA et al (2005) Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol 32(12):2485–2487

    PubMed  Google Scholar 

  29. Szkudlarek M, Court-Payen M, Jacobsen S, Klarlund M, Thomsen HS, Østergaard M (2003) Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis. Arthritis Rheum 48(4):955–962

    Article  PubMed  Google Scholar 

  30. Naredo E, Möller I, Cruz A, Carmona L, Garrido J (2008) Power Doppler ultrasonographic monitoring of response to anti-tumor necrosis factor therapy in patients with rheumatoid arthritis. Arthritis Rheum 58(8):2248–2256. doi:10.1002/art.23682

    Article  PubMed  Google Scholar 

  31. Naredo E, D’Agostino MA, Wakefield RJ, Möller I, Balint PV, Filippucci E, Iagnocco A, Karim Z, Terslev L, Bong DA, Garrido J, Martínez-Hernández D, Bruyn GA, Ultrasound Task Force OMERACT (2013) Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid arthritis. Ann Rheum Dis 72(8):1328–1334. doi:10.1136/annrheumdis-2012-202092

    Article  PubMed  Google Scholar 

  32. Naredo E, Rodríguez M, Campos C, Rodríguez-Heredia JM, Medina JA, Giner E et al (2008) Validity, reproducibility, and responsiveness of a twelve-joint simplified power Doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis. Arthritis Rheum 59(4):515–522. doi:10.1002/art.23529

    Article  PubMed  Google Scholar 

  33. Backhaus M, Ohrndorf S, Kellner H, Strunk J, Backhaus TM, Hartung W, Sattler H, Albrecht K, Kaufmann J, Becker K, Sörensen H, Meier L, Burmester GR, Schmidt WA (2009) Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum 61(9):1194–1201. doi:10.1002/art.24646

    Article  CAS  PubMed  Google Scholar 

  34. Perricone C, Ceccarelli F, Modesti M, Vavala C, Di Franco M, Valesini G, Iagnocco A (2012) The 6-joint ultrasonographic assessment: a valid, sensitive-to-change and feasible method for evaluating joint inflammation in RA. Rheumatology 51(5):866–873. doi:10.1093/rheumatology/ker405

    Article  PubMed  Google Scholar 

  35. Prevoo ML, van Gestel AM, van THof MA, van Rijswijk MH, van de Putte LB, van Riel PL (1996) Remission in a prospective study of patients with rheumatoid arthritis. American Rheumatism Association preliminary remission criteria in relation to the disease activity score. Br J Rheumatol 35(11):1101–1105

    Article  CAS  PubMed  Google Scholar 

  36. Bingham CO 3rd, Pohl C, Woodworth TG, Hewlett SE, May JE, Rahman MU, Witter JP, Furst DE, Strand CV, Boers M, Alten RE (2009) Developing a standardized definition for disease “flare” in rheumatoid arthritis (OMERACT 9 Special Interest Group). J Rheumatol 36(10):2335–2341. doi:10.3899/jrheum.090369

    Article  PubMed  Google Scholar 

  37. Mierau M, Schoels M, Gonda G, Fuchs J, Aletaha D, Smolen JS (2007) Assessing remission in clinical practice. Rheumatology 46(6):975–979

    Article  CAS  PubMed  Google Scholar 

  38. Sokka T, Hetland ML, Mäkinen H, Kautiainen H, Hørslev-Petersen K, Luukkainen RK et al (2008) Questionnaires in standard monitoring of patients with Rheumatoid Arthritis group. Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four countries. Arthritis Rheum 58(9):2642–2651. doi:10.1002/art.23794

    Article  PubMed  Google Scholar 

  39. Prince FH, Bykerk VP, Shadick NA, Lu B, Cui J, Frits M, Iannaccone CK, Weinblatt ME, Solomon DH (2012) Sustained rheumatoid arthritis remission is uncommon in clinical practice. Arthritis Res Ther 14(2):R68. doi:10.1186/ar3785

    Article  PubMed Central  PubMed  Google Scholar 

  40. Molenaar ET, Voskuyl AE, Dinant HJ, Bezemer PD, Boers M, Dijkmans BA (2004) Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum 50(1):36–42

    Article  PubMed  Google Scholar 

  41. Boutry N, Lardé A, Lapègue F, Solau-Gervais E, Flipo RM, Cotten A (2003) Magnetic resonance imaging appearance of the hands and feet in patients with early rheumatoid arthritis. J Rheumatol 30(4):671–679

    PubMed  Google Scholar 

  42. Eshed I, Feist E, Althoff CE, Hamm B, Konen E, Burmester GR, Backhaus M, Hermann KG (2009) Tenosynovitis of the flexor tendons of the hand detected by MRI: an early indicator of rheumatoid arthritis. Rheumatology 48(8):887–891. doi:10.1093/rheumatology/kep136

    Article  PubMed  Google Scholar 

  43. Navalho M, Resende C, Rodrigues AM, Ramos F, Gaspar A, Pereira da Silva JA, Fonseca JE, Campos J, Canhão H (2012) Bilateral MR imaging of the hand and wrist in early and very early inflammatory arthritis: tenosynovitis is associated with progression to rheumatoid arthritis. Radiology 264(3):823–833. doi:10.1148/radiol.12112513

    Article  PubMed  Google Scholar 

  44. Schmidt WA, Schicke B, Ostendorf B, Scherer A, Krause A, Walther M (2013) Low-field MRI versus ultrasound: which is more sensitive in detecting inflammation and bone damage in MCP and MTP joints in mild or moderate rheumatoid arthritis? Clin Exp Rheumatol 31(1):91–96

    PubMed  Google Scholar 

  45. Wakefield RJ, O’Connor PJ, Conaghan PG, McGonagle D, Hensor EM, Gibbon WW, Brown C, Emery P (2007) Finger tendon disease in untreated early rheumatoid arthritis: a comparison of ultrasound and magnetic resonance imaging. Arthritis Rheum 57(7):1158–1164

    Article  CAS  PubMed  Google Scholar 

  46. Wakefield RJ, Freeston JE, O’Connor P, Reay N, Budgen A, Hensor EM, Helliwell PS, Emery P, Woodburn J (2008) The optimal assessment of the rheumatoid arthritis hindfoot: a comparative study of clinical examination, ultrasound and high field MRI. Ann Rheum Dis 67(12):1678–1682. doi:10.1136/ard.2007.079947

    Article  CAS  PubMed  Google Scholar 

  47. Hammer HB, Kvien TK (2011) Ultrasonography shows significant improvement in wrist and ankle tenosynovitis in rheumatoid arthritis patients treated with adalimumab. Scand J Rheumatol 40:178–182

    Article  CAS  PubMed  Google Scholar 

  48. Lillegraven S, Bøyesen P, Hammer HB, Østergaard M, Uhlig T, Sesseng S, Kvien TK, Haavardsholm EA (2011) Tenosynovitis of the extensor carpi ulnaris tendon predicts erosive progression in early rheumatoid arthritis. Ann Rheum Dis 70(11):2049–2050. doi:10.1136/ard.2011.151316

    Article  PubMed  Google Scholar 

Download references

Author contributions

Esperanza Naredo, Inmaculada De La Torre, Lara Valor, and Iustina Janta designed the study. Esperanza Naredo, Inmaculada De La Torre, Lara Valor, Iustina Janta, Lina Martínez-Estupiñán, Juan Carlos Nieto, Juan Gabriel Ovalles-Bonilla, Julia Martínez-Barrio, Natalia Bello, Michelle Hinojosa, María Montoro, Carlos Manuel González, Javier López-Longo, and Indalecio Monteagudo involved in data acquisition. Esperanza Naredo, Inmaculada De La Torre, Lara Valor, and Luis Carreño interpreted and analyzed the data. Esperanza Naredo, Iustina Janta, Inmaculada De La Torre, and Lara Valor prepared the manuscript.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Faculty of Medicine, Hospital General Universitario Gregorio Marañón, Complutense University, Doctor Esquerdo 46, 28007, Madrid, Spain

    Iustina Janta, Lara Valor, Inmaculada De la Torre, Lina Martínez-Estupiñán, Juan Carlos Nieto, Juan Gabriel Ovalles-Bonilla, Julia Martínez-Barrio, Natalia Bello, Michelle Hinojosa, María Montoro, Carlos Manuel González, Javier López-Longo, Indalecio Monteagudo, Luis Carreño & Esperanza Naredo

Authors
  1. Iustina Janta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lara Valor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Inmaculada De la Torre
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lina Martínez-Estupiñán
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juan Carlos Nieto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Juan Gabriel Ovalles-Bonilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Julia Martínez-Barrio
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Natalia Bello
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michelle Hinojosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. María Montoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Carlos Manuel González
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Javier López-Longo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Indalecio Monteagudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Luis Carreño
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Esperanza Naredo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iustina Janta.

Ethics declarations

Conflict of interest

Lara Valor has received speaker fees from Abbvie, Roche Farma, Bristol-Myers Squibb, and Pfizer. Juan Carlos Nieto-González has received speaker fees from Abbvie, Roche Farma, Pfizer, MSD. Francisco Javier López-Longo has received speaker fees from Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, MSD, Actelion. Francisco Javier López-Longo has received research funding from Abbvie and GSK. Indalecio Monteagudo has received speaker fees from Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, and UCB. Esperanza Naredo has received speaker fees from Abbvie, Roche Farma, Bristol-Myers Squibb, Pfizer, UCB, and Novartis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Janta, I., Valor, L., De la Torre, I. et al. Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints and tendons should be assessed to predict unstable remission?. Rheumatol Int 36, 387–396 (2016). https://doi.org/10.1007/s00296-015-3409-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-015-3409-8

Keywords

Search

Navigation