Advertisement

Rheumatology International

, Volume 38, Issue 8, pp 1465–1470 | Cite as

Identifying markers of sustained remission in rheumatoid arthritis patients on long-term tapered biological disease-modifying antirheumatic drugs

  • Lara Valor
  • Jesús Garrido
  • Lina Martínez-Estupiñán
  • Diana Hernández-Flórez
  • Iustina Janta
  • Francisco Javier López-Longo
  • Indalecio Monteagudo
  • Carlos M. González
  • Esperanza Naredo
Biomarkers
  • 74 Downloads

Abstract

To identify features associated with long-term persistent remission in rheumatoid arthritis (RA) patients on tapered biological disease-modifying antirheumatic drugs (bDMARD) (tap-bDMARD) therapy. We carried out a 40-month (m) extension follow-up study of 77 RA patients from a previous 12 m tap-bDMARD study. Disease activity was assessed at baseline and every 3 months. Doppler US investigation of 42 joints for the presence and grade (0–3) of B-mode synovial hypertrophy (SH) and synovial power Doppler signal (i.e., Doppler synovitis) was performed before starting the tap-bDMARD strategy by a rheumatologist blinded to clinical and laboratory data. At the 40 m mark, 44 (57.1%) patients failed the tap-bDMARD strategy, while 33 (42.9%) succeeded. Patients who presented a failed tap-bDMARD had significantly longer disease duration, a longer time from symptom onset to synthetic (s) DMARD start, longer duration of sDMARD treatment, a greater number of sDMARDs, and a higher baseline DAS28 and SDAI than patients with successful tap-bDMARD at 40 months. In logistic regression analysis, the presence of baseline Doppler synovitis, a DAS28 ≥ 2.2, and the presence of rheumatoid factor were identified as predictors of tap-bDMARD failure at 40 m. In those patients who succeed tap-bDMARD at 12 m, a smoking habit was significantly more frequently found in tap-bDMARD failures at 40 m. Our results showed that DAS28 and the presence of Doppler synovitis, RF and a smoking habit predicted long-term tap-bDMARD failure.

Keywords

Rheumatoid arthritis Biologic therapy Tapering Musculoskeletal ultrasound 

Notes

Acknowledgements

The authors would like to thank all patients who kindly consented to participate in this study and the Spanish Society of Rheumatology for their support throughout the manuscript preparation process.

Author contributions

E.N., L.V., J.G.: study design. E.N, L.V., I.J. I.M., F.J.L.-L., D.H-F., C.G.: acquisition of data. E.N., L.V., L.M-E., J.G.: analysis and interpretation of data. E.N., L.V., L.M-E., J.G.: manuscript preparation.

Funding

The authors received no specific funding for this work.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Yoshida K, Sung YK, Kavanaugh A, Bae SC, Weinblatt ME, Kishimoto M, Matsui K, Tohma S, Solomon DH (2014) Biologic discontinuation studies: a systematic review of methods. Ann Rheum Dis 73:595–599CrossRefPubMedGoogle Scholar
  2. 2.
    Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, Boers M, Buckley CD, Buttgereit F, Bykerk V, Cardiel M, Combe B, Cutolo M, van Eijk-Hustings Y, Emery P, Finckh A, Gabay C, Gomez-Reino J, Gossec L, Gottenberg JE, Hazes JMW, Huizinga T, Jani M, Karateev D, Kouloumas M, Kvien T, Li Z, Mariette X, McInnes I, Mysler E, Nash P, Pavelka K, Poór G, Richez C, van Riel P, Rubbert-Roth A, Saag K, da Silva J, Stamm T, Takeuchi T, Westhovens R (2017) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 76(6):960–977CrossRefPubMedGoogle Scholar
  3. 3.
    Schett G, Emery P, Tanaka Y, Burmester G, Pisetsky DS, Naredo E, Fautrel B, van Vollenhoven R (2016) Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis 75(8):1428–1437CrossRefPubMedGoogle Scholar
  4. 4.
    Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O’Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T, American College of Rheumatology (2016) 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 68(1):1–25CrossRefGoogle Scholar
  5. 5.
    Naredo E, Valor L, De la Torre I, Montoro M, Bello N, Martínez-Barrio J, Martínez-Estupiñán L, Nieto JC, Ovalles-Bonilla JG, Hernández-Flórez D, González CM, López-Longo FJ, Monteagudo I, Carreño L (2015) Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis. Rheumatology (Oxford) 54(8):1408–1414CrossRefGoogle Scholar
  6. 6.
    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 65:512–517CrossRefGoogle Scholar
  7. 7.
    Naredo E, Rodriguez M, Campos C et al Rodríguez-Heredia JM, Medina JA, Giner E, Martínez O, Toyos FJ, Ruíz T, Ros I, Pujol M, Miquel X, García L, Aznar JJ, Chamizo E, Páez M, Morales P, Rueda A, Tuneu R, Corominas H, de Agustín JJ, Moragues C, Mínguez D, Willisch A, González-Cruz I, Aragón A, Iglesias G, Armas C, Pablo Valdazo J, Vargas C, Calvo-Alén J, Juan-Mas A, Salvador G, Puigdollers A, Galíndez E, Garrido N, Salaberri J, Raya E, Salles M, Díaz C, Cuadra JL, Garrido J, Ultrasound Group of The Spanish Society of Rheumatology (2008) Validity, reproducibility and responsiveness of a 12-joint simplified power Doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis. Arthritis Rheum 59:512–22CrossRefGoogle Scholar
  8. 8.
    Wakefield RJ, Balint P, Szkudlarek M, Filippucci E, Backhaus M, D’Agostino MA, Sanchez EN, Iagnocco A, Schmidt WA, Bruyn GA, Kane D, O’Connor PJ, Manger B, Joshua F, Koski J, Grassi W, Lassere MN, Swen N, Kainberger F, Klauser A, Ostergaard M, Brown AK, Machold KP, Conaghan PG, OMERACT 7 Special Interest Group (2015) Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol 32:2485 7Google Scholar
  9. 9.
    D’Agostino MA, Terslev L, Aegerter P, Backhaus M, Balint P, Bruyn GA, Filippucci E, Grassi W, Iagnocco A, Jousse-Joulin S, Kane D, Naredo E, Schmidt W, Szkudlarek M, Conaghan PG, Wakefield RJ (2017) Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce Part 1: definition and development of a standardised, consensus-based scoring system. RMD Open 3(1):e000428CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Terslev L, Naredo E, Aegerter P, Wakefield RJ, Backhaus M, Balint P, Bruyn GAW, Iagnocco A, Jousse-Joulin S, Schmidt WA, Szkudlarek M, Conaghan PG, Filippucci E, D’Agostino MA (2017) Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 2: reliability and application to multiple joints of a standardised consensus-based scoring system. RMD Open 11;3(1):e000427CrossRefGoogle Scholar
  11. 11.
    Smolen JS, Nash P, Durez P, Hall S, Ilivanova E, Irazoque-Palazuelos F, Miranda P, Park MC, Pavelka K, Pedersen R, Szumski A, Hammond C, Koenig AS, Vlahos B (2013) Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomized controlled trial. Lancet 381:918 29CrossRefPubMedGoogle Scholar
  12. 12.
    Van der Maas A, Kievit W, Van den Bemt BJF, van den Hoogen FH, van Riel PL, den Broeder AA (2012) Down-titration and discontinuation of infliximab in rheumatoid arthritis patients with stable low disease activity and stable treatment: an observational cohort study. Ann Rheum Dis 71:1849 54PubMedGoogle Scholar
  13. 13.
    van Vollenhoven RF, Østergaard M, Leirisalo-Repo M, Uhlig T, Jansson M, Larsson E, Brock F, Franck-Larsson K (2016) Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis. Ann Rheum Dis 75(1):52–8CrossRefPubMedGoogle Scholar
  14. 14.
    Haschka J, Englbrecht M, Hueber AJ, Manger B, Kleyer A, Reiser M, Finzel S, Tony HP, Kleinert S, Feuchtenberger M, Fleck M, Manger K, Ochs W, Schmitt-Haendle M, Wendler J, Schuch F, Ronneberger M, Lorenz HM, Nuesslein H, Alten R, Demary W, Henes J, Schett G, Rech J (2016) Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis 75(1):45–51CrossRefPubMedGoogle Scholar
  15. 15.
    Tanaka Y, Hirata S, Kubo S, Fukuyo S, Mizuno Y, Iwata S, Nawata M, Sawamukai N, Nakano K, Yamaoka K, Tanaka Y (2015) Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study. Ann Rheum Dis 74(2):389–95CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Lara Valor
    • 1
  • Jesús Garrido
    • 2
  • Lina Martínez-Estupiñán
    • 1
  • Diana Hernández-Flórez
    • 1
  • Iustina Janta
    • 1
  • Francisco Javier López-Longo
    • 1
  • Indalecio Monteagudo
    • 1
  • Carlos M. González
    • 1
  • Esperanza Naredo
    • 3
  1. 1.Department of Rheumatology, Hospital General Universitario Gregorio Marañón, Faculty of MedicineUniversidad ComplutenseMadridSpain
  2. 2.Department of Social Psychology and MethodologyUniversidad Autónoma de MadridMadridSpain
  3. 3.Department of Rheumatology, Joint and Bone Research UnitHospital Universitario Fundación Jiménez DíazMadridSpain

Personalised recommendations