Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2016

Open Access 01-12-2016 | Research article

Tapering and discontinuation of TNF-α blockers without disease relapse using ultrasonography as a tool to identify patients with rheumatoid arthritis in clinical and histological remission

Authors: Stefano Alivernini, Giusy Peluso, Anna Laura Fedele, Barbara Tolusso, Elisa Gremese, Gianfranco Ferraccioli

Published in: Arthritis Research & Therapy | Issue 1/2016

Login to get access

Abstract

Background

In this study, we assessed whether clinical and ultrasonography (US)-based remission could be used to select patients with rheumatoid arthritis (RA) eligible to taper and discontinue anti-TNF-α therapy after achievement of remission, looking at disease relapse.

Methods

Forty-two patients with RA in sustained remission who were receiving anti-TNF-α treatment (Disease Activity Score <1.6 at three visits 3 months apart) underwent US evaluation of synovial hypertrophy (SH) and power Doppler (PD) signal presence. Five SH+/PD− patients with RA underwent US-guided knee synovial tissue biopsy to assess histological features of residual synovitis (CD68, CD3 and CD20 immunostaining) after sustained clinical remission was achieved. All patients were enrolled to taper first then discontinue anti-TNF-α. They were followed every 3 months afterwards, and the relapse rate was recorded.

Results

Selected SH+/PD− patients showed low-grade synovitis as demonstrated by the presence of CD68+ cells in the lining layer and few infiltrating CD3+ and CD20+ cells at the time sustained clinical remission was achieved. After anti-TNF-α tapering, 13 patients (30.9 %) relapsed and 29 (69.1 %) SH+/PD− patients maintained disease remission after 3 months and discontinued anti-TNF-α treatment. Among them, 26 patients (89.7 %) maintained disease remission status after 6 months of follow-up. All patients who relapsed were retreated with the previous biologic, following the last effective therapeutic regimen, again reaching a good European League Against Rheumatism response within 3 months.

Conclusions

US evaluation using PD signalling allows the identification of patients with RA in clinical and histological remission after tapering and discontinuing biologics.
Appendix
Available only for authorised users
Literature
1.
go back to reference Yoshimi R, Hama M, Takase K, Ihata A, Kishimoto D, Terauchi K, et al. Ultrasonography is a potent tool for the prediction of progressive joint destruction during clinical remission of rheumatoid arthritis. Mod Rheum. 2012;23:456–65.CrossRef Yoshimi R, Hama M, Takase K, Ihata A, Kishimoto D, Terauchi K, et al. Ultrasonography is a potent tool for the prediction of progressive joint destruction during clinical remission of rheumatoid arthritis. Mod Rheum. 2012;23:456–65.CrossRef
2.
go back to reference Molenaar ET, Voskuyl AE, Dinant HJ, Bezemer PD, Boers M, Dijkmans BA. Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum. 2004;50:36–42.CrossRefPubMed Molenaar ET, Voskuyl AE, Dinant HJ, Bezemer PD, Boers M, Dijkmans BA. Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum. 2004;50:36–42.CrossRefPubMed
3.
go back to reference Cheung PP, Dougados M, Gossec L. Reliability of ultrasonography to detect synovitis in rheumatoid arthritis: a systematic literature review of 35 studies (1,415 patients). Arthritis Care Res (Hoboken). 2010;62:323–34.CrossRef Cheung PP, Dougados M, Gossec L. Reliability of ultrasonography to detect synovitis in rheumatoid arthritis: a systematic literature review of 35 studies (1,415 patients). Arthritis Care Res (Hoboken). 2010;62:323–34.CrossRef
4.
go back to reference Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, et al. 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. 2006;54:3761–73.CrossRefPubMed Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, et al. 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. 2006;54:3761–73.CrossRefPubMed
5.
go back to reference Peluso G, Michelutti A, Bosello SL, Gremese E, Tolusso B, Ferraccioli G. Clinical and ultrasonographic remission determines different chances of relapse in early and long standing rheumatoid arthritis. Ann Rheum Dis. 2011;7:172–5.CrossRef Peluso G, Michelutti A, Bosello SL, Gremese E, Tolusso B, Ferraccioli G. Clinical and ultrasonographic remission determines different chances of relapse in early and long standing rheumatoid arthritis. Ann Rheum Dis. 2011;7:172–5.CrossRef
6.
go back to reference Ollendorf DA, Klingman D, Hazard E, Ray S. Differences in annual medication costs and rates of dosage increase between tumor necrosis factor-antagonist therapies for rheumatoid arthritis in a managed care population. Clin Ther. 2009;31:825–35.CrossRefPubMed Ollendorf DA, Klingman D, Hazard E, Ray S. Differences in annual medication costs and rates of dosage increase between tumor necrosis factor-antagonist therapies for rheumatoid arthritis in a managed care population. Clin Ther. 2009;31:825–35.CrossRefPubMed
7.
go back to reference Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295:2275–85.CrossRefPubMed Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295:2275–85.CrossRefPubMed
8.
go back to reference Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 3rd CO, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569–81.CrossRefPubMed Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 3rd CO, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569–81.CrossRefPubMed
9.
go back to reference Alten R, Pohl C, Choy EH, Christensen R, Furst DE, Hewlett SE, et al. Developing a construct to evaluate flares in rheumatoid arthritis: a conceptual report of the OMERACT RA Flare Definition Working Group. J Rheumatol. 2011;38:1745–50.CrossRefPubMed Alten R, Pohl C, Choy EH, Christensen R, Furst DE, Hewlett SE, et al. Developing a construct to evaluate flares in rheumatoid arthritis: a conceptual report of the OMERACT RA Flare Definition Working Group. J Rheumatol. 2011;38:1745–50.CrossRefPubMed
10.
go back to reference Humby F, Kelly S, Bugatti S, Manzo A, Filer A, Mahto A, et al. Evaluation of minimally invasive, ultrasound-guided synovial biopsy techniques by the OMERACT filter-determining validation requirements. J Rheumatol. 2016;43:208–13.CrossRefPubMed Humby F, Kelly S, Bugatti S, Manzo A, Filer A, Mahto A, et al. Evaluation of minimally invasive, ultrasound-guided synovial biopsy techniques by the OMERACT filter-determining validation requirements. J Rheumatol. 2016;43:208–13.CrossRefPubMed
11.
go back to reference Nguyen H, Ruyssen-Witrand A, Gandjbakhch F, Constantin A, Foltz V, Cantagrel A. Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural progression in rheumatoid arthritis patients in clinical remission: a systematic review and meta-analysis. Rheumatology (Oxford). 2014;53:2110–8.CrossRef Nguyen H, Ruyssen-Witrand A, Gandjbakhch F, Constantin A, Foltz V, Cantagrel A. Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural progression in rheumatoid arthritis patients in clinical remission: a systematic review and meta-analysis. Rheumatology (Oxford). 2014;53:2110–8.CrossRef
12.
go back to reference Anandarajah A, Thiele R, Giampoli E, Monu J, Seo GS, Feng C, et al. Patients with rheumatoid arthritis in clinical remission manifest persistent joint inflammation on histology and imaging studies. J Rheumatol. 2014;41:2153–60.CrossRefPubMed Anandarajah A, Thiele R, Giampoli E, Monu J, Seo GS, Feng C, et al. Patients with rheumatoid arthritis in clinical remission manifest persistent joint inflammation on histology and imaging studies. J Rheumatol. 2014;41:2153–60.CrossRefPubMed
13.
go back to reference Singh JA, Arayssi T, Duray P, Schumacher HR. Immunohistochemistry of normal human knee synovium: a quantitative study. Ann Rheum Dis. 2004;63:785–90.PubMedCentralCrossRefPubMed Singh JA, Arayssi T, Duray P, Schumacher HR. Immunohistochemistry of normal human knee synovium: a quantitative study. Ann Rheum Dis. 2004;63:785–90.PubMedCentralCrossRefPubMed
14.
go back to reference Della Beffa C, Slansky E, Pommerenke C, Klawonn F, Li J, Dai L, et al. The relative composition of the inflammatory infiltrate as an additional tool for synovial tissue classification. PLoS One. 2013;8:e72494.PubMedCentralCrossRefPubMed Della Beffa C, Slansky E, Pommerenke C, Klawonn F, Li J, Dai L, et al. The relative composition of the inflammatory infiltrate as an additional tool for synovial tissue classification. PLoS One. 2013;8:e72494.PubMedCentralCrossRefPubMed
15.
go back to reference Naredo E, Valor L, De la Torre I, Montoro M, Bello N, Martínez-Barrio J, et al. Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis. Rheumatology (Oxford). 2015;54:1408–14.CrossRef Naredo E, Valor L, De la Torre I, Montoro M, Bello N, Martínez-Barrio J, et al. Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis. Rheumatology (Oxford). 2015;54:1408–14.CrossRef
16.
go back to reference Smolen JS, Nash P, Durez P, Hall S, Ilivanova E, Irazoque-Palazuelos F, et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet. 2013;381:918–29.CrossRefPubMed Smolen JS, Nash P, Durez P, Hall S, Ilivanova E, Irazoque-Palazuelos F, et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet. 2013;381:918–29.CrossRefPubMed
17.
go back to reference Naredo E, Valor L, De la Torre I, Martínez-Barrio J, Hinojosa M, Aramburu F, et al. Ultrasound joint inflammation in rheumatoid arthritis in clinical remission: how many and which joints should be assessed? Arthritis Care Res. 2013;65:512–7.CrossRef Naredo E, Valor L, De la Torre I, Martínez-Barrio J, Hinojosa M, Aramburu F, et al. Ultrasound joint inflammation in rheumatoid arthritis in clinical remission: how many and which joints should be assessed? Arthritis Care Res. 2013;65:512–7.CrossRef
18.
go back to reference 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;43:1927–40.CrossRefPubMed 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;43:1927–40.CrossRefPubMed
19.
go back to reference Ikeda K, Seto Y, Narita A, Kawakami A, Kawahito Y, Ito H, et al. Ultrasound assessment of synovial pathologic features in rheumatoid arthritis using comprehensive multiplane images of the second metacarpophalangeal joint: identification of the components that are reliable and influential on the global assessment of the whole joint. Arthritis Rheumatol. 2014;66:523–32.CrossRefPubMed Ikeda K, Seto Y, Narita A, Kawakami A, Kawahito Y, Ito H, et al. Ultrasound assessment of synovial pathologic features in rheumatoid arthritis using comprehensive multiplane images of the second metacarpophalangeal joint: identification of the components that are reliable and influential on the global assessment of the whole joint. Arthritis Rheumatol. 2014;66:523–32.CrossRefPubMed
20.
go back to reference Navarro-Millán I, Sattui SE, Curtis JR. Systematic review of tumor necrosis factor inhibitor discontinuation studies in rheumatoid arthritis. Clin Ther. 2013;35:1850–61.PubMedCentralCrossRefPubMed Navarro-Millán I, Sattui SE, Curtis JR. Systematic review of tumor necrosis factor inhibitor discontinuation studies in rheumatoid arthritis. Clin Ther. 2013;35:1850–61.PubMedCentralCrossRefPubMed
Metadata
Title
Tapering and discontinuation of TNF-α blockers without disease relapse using ultrasonography as a tool to identify patients with rheumatoid arthritis in clinical and histological remission
Authors
Stefano Alivernini
Giusy Peluso
Anna Laura Fedele
Barbara Tolusso
Elisa Gremese
Gianfranco Ferraccioli
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-016-0927-z

Other articles of this Issue 1/2016

Arthritis Research & Therapy 1/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.