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

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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.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-016-0927-z) contains supplementary material, which is available to authorized users.

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Most cited references 15

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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.

P J Conaghan, C Peterfy, Sarah A E Brown … (2006)

More timely and effective therapy for rheumatoid arthritis (RA) has contributed to increasing rates of clinical remission. However, progression of structural damage may still occur in patients who have satisfied remission criteria, which suggests that there is ongoing disease activity. This questions the validity of current methods of assessing remission in RA. The purpose of this study was to test the hypothesis that modern joint imaging improves the accuracy of remission measurement in RA. We studied 107 RA patients receiving disease-modifying antirheumatic drug therapy who were judged by their consultant rheumatologist to be in remission and 17 normal control subjects. Patients underwent clinical, laboratory, functional, and quality of life assessments. The Disease Activity Score 28-joint assessment and the American College of Rheumatology remission criteria, together with strict clinical definitions of remission, were applied. Imaging of the hands and wrists using standardized acquisition and scoring techniques with conventional 1.5T magnetic resonance imaging (MRI) and ultrasonography (US) were performed. Irrespective of which clinical criteria were applied to determine remission, the majority of patients continued to have evidence of active inflammation, as shown by findings on the imaging assessments. Even in asymptomatic patients with clinically normal joints, MRI showed that 96% had synovitis and 46% had bone marrow edema, and US showed that 73% had gray-scale synovial hypertrophy and 43% had increased power Doppler signal. Only mild synovial thickening was seen in 3 of the control subjects (18%), but no bone marrow edema. Most RA patients who satisfied the remission criteria with normal findings on clinical and laboratory studies had imaging-detected synovitis. This subclinical inflammation may explain the observed discrepancy between disease activity and outcome in RA. Imaging assessment may be necessary for the accurate evaluation of disease status and, in particular, for the definition of true remission.

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Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission.

P Bezemer, B. A. C. Dijkmans, Alexandre E Voskuyl … (2003)

To assess whether radiologic progression occurs during clinical remission in patients with rheumatoid arthritis (RA). One hundred eighty-seven patients with RA in clinical remission were followed up clinically and radiologically for 2 years. Clinical remission was defined according to a modification of the American College of Rheumatology criteria (i.e., the criterion of fatigue was omitted, and patients had to fulfill 4 of the 5 remaining criteria). Radiologic joint damage was assessed by the Sharp/van der Heijde method. After 2 years of followup, remission persisted in 52% of patients. The median radiologic score for the total group of patients increased from 21 (interquartile range [IQR] 5, 65) at the time of entry to 25 (IQR 7, 72) after 2 years (P < 0.001). The median score for radiologic progression between baseline and 2 years was 0.5 (IQR 0, 2.5). Among patients with an exacerbation of RA (n = 86), the median score for progression over 2 years was 1.0 (IQR 0, 4.5) (P < 0.001), and in patients with a persistent remission (n = 93) it was 0 (IQR -0.5, 2.0) (P < 0.001). Clinically relevant progression of damage was more frequent in patients with exacerbation (23%) than in those with persistent remission (7%) (P = 0.001). However, in 15% of patients with persistent remission, an erosion developed in a previously unaffected joint. In the logistic regression analysis, the area under the curve of the Disease Activity Score, a continuous measure, was related to the chance of radiologic progression, regardless of the absolute disease activity level. Results were similar when other definitions of remission were used. Although rare, clinically relevant progression of joint damage does occur in patients with RA in prolonged remission. This suggests the need for markers that predict progression during periods of low disease activity and for drugs that prevent damage that is independent of disease activity.

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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.

Huong Nguyen, Adeline Ruyssen-Witrand, Frédérique Gandjbakhch … (2014)

The aims of this study were to assess the prevalence of US-detected residual synovitis in patients with RA in clinical remission (CR) and evaluate its predictive value for relapse and structural progression.

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Author and article information

Contributors

Stefano Alivernini: stefano.alivernini@hotmail.it

Giusy Peluso: giusy.peluso@h-columbus.it

Anna Laura Fedele: annalaurafedele@gmail.com

Barbara Tolusso: barbara.tolusso@rm.unicatt.it

Elisa Gremese: elisa.gremese@rm.unicatt.it

Gianfranco Ferraccioli: gf.ferraccioli@rm.unicatt.it

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res. Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central (London )

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Electronic): 3 February 2016

Publication date PMC-release: 3 February 2016

Publication date (Print): 2016

Volume: 18

Electronic Location Identifier: 39

Affiliations

[ ]Institute of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy

[ ]Division of Rheumatology, Institute of Rheumatology and Affine Sciences, Complesso Integrato Columbus, Via Giuseppe Moscati, 31, 00168 Rome, Italy

Article

Publisher ID: 927

DOI: 10.1186/s13075-016-0927-z

PMC ID: 4741059

PubMed ID: 26842890

SO-VID: 7c285abd-6fd4-46f0-a094-6bb154e2979c

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 20 August 2015

Date accepted : 7 January 2016

Custom metadata

ScienceOpen disciplines: Orthopedics

Keywords: rheumatoid arthritis,synovial tissue,ultrasonography assessment,disease remission,anti-tnf-α agents,discontinuation,disease relapse

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ScienceOpen disciplines: Orthopedics

Keywords: rheumatoid arthritis, synovial tissue, ultrasonography assessment, disease remission, anti-tnf-α agents, discontinuation, disease relapse

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

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Most cited references 15

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.

Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission.

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.

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