Predictive role of ultrasound remission for progressive ultrasonography-detected structural damage in patients with rheumatoid arthritis

2021 ◽  
pp. jim-2021-001885
Author(s):  
Feifei Liu ◽  
Wenxue Li ◽  
Jiaan Zhu ◽  
Fang Liu ◽  
Wenting Fan ◽  
...  

Regarding the persistence of subclinical synovitis, the concept of ultrasound remission has been proposed in addition to clinical remission. However, there have been no studies that explored the different time points of ultrasound remission to predict non-progressive structural damage. Given this, the aim of our study is to explore whether early ultrasound remission in patients with rheumatoid arthritis (RA) has predictive value for non-progressive structural damage in the subsequent 12 months. Sixty-one patients with RA were prospectively studied. Synovial hypertrophy, power Doppler (PD) signal, and bone erosions of bilateral wrists, metacarpophalangeal joints I–V, and proximal interphalangeal joints II–III were assessed by ultrasonography at baseline and at 3, 6, and 12 months. Ultrasound remission was defined as no PD signal. Clinical remission was defined as Disease Activity Score in 28 Joints <2.6. Ultrasonography-detected joint damage progression was defined as increase in bone erosion score of ≥1 in the subsequent 12 months. Baseline ultrasonographic factors were not significantly correlated with progressive ultrasonography-detected joint damage in patients with RA at 12 months (all p>0.05). Ultrasound remission at 3 and 6 months was significantly correlated with non-progressive ultrasonography-detected structural damage at 12 months (p=0.006 and p=0.004), with relatively low sensitivity and high specificity. Clinical remission at 3 months was significantly correlated with non-progression of ultrasonography-detected structural damage at 12 months (p=0.029), with relatively low sensitivity and moderate specificity. Ultrasound remission at 3 and 6 months has high specificity in predicting non-progressive structural damage in patients with RA at 12 months; however, the sensitivity is limited.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 583-583
Author(s):  
C. Garufi ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
S. Mancuso ◽  
C. Pirone ◽  
...  

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos


2021 ◽  
Vol 22 (24) ◽  
pp. 13290
Author(s):  
Cristina García-Moreno ◽  
María J. Gómara ◽  
Raúl Castellanos-Moreira ◽  
Raimon Sanmartí ◽  
Isabel Haro

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.


2021 ◽  
pp. annrheumdis-2020-218744
Author(s):  
Irina Gessl ◽  
Mihaela Popescu ◽  
Victoria Schimpl ◽  
Gabriela Supp ◽  
Thomas Deimel ◽  
...  

ObjectivesTo determine whether clinical tenderness can be considered a sign of inflammatory joint activity in patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PsA) and to assess other possible factors associated with tenderness.MethodsPatients diagnosed with RA, PsA and OA underwent clinical and ultrasound examination of wrists and finger joints. Radiographs of the hands were scored for erosions, joint space narrowing (JSN), osteophytes and malalignment. A binary damage score (positive if ≥1 erosion, JSN and/or presence of malalignment) was calculated. Differences in grey scale signs of synovitis and power Doppler (PD) between tender non-swollen (TNS) versus non-tender non-swollen (NTNS) joints were calculated. Disease duration was assessed,<2 years was regarded as early and >5 years as long-standing arthritis.ResultsIn total, 34 patients (9 early and 14 long-standing) from patients with RA, 31 patients (7 early and 15 long-standing) with PsA and 30 with OA were included. We found equal frequencies of PD signal between TNS and NTNS joints in RA (p=0.18), PsA (p=0.59) or OA (p=0.96). However, PD had a significant association with tenderness in early arthritis both in RA (p=0.02) and in PsA (p=0.02). The radiographic damage score showed significant association with tenderness in RA (p<0.01), PsA (p<0.01) and OA (p=0.04).ConclusionTenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.


2018 ◽  
Vol 77 (9) ◽  
pp. 1283-1289 ◽  
Author(s):  
Georgios Filippou ◽  
Garifallia Sakellariou ◽  
Carlo Alberto Scirè ◽  
Greta Carrara ◽  
Federica Rumi ◽  
...  

ObjectiveTo define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation.MethodsA multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres participated, enrolling consecutive patients with RA in clinical remission. All patients underwent complete clinical assessment (demographic data, disease characteristics, laboratory exams, clinical assessment of 28 joints and patient/physician-reported outcomes) and Power Doppler (PD) US evaluation of wrist, metacarpalphalangeal joints, proximal interphalangeal joints and synovial tendons of the hands and wrists at enrolment, 6 and 12 months. The association between clinical and US variables with flare, disability and radiographic progression was evaluated by univariable and adjusted logistic regression models.Results361 patients were enrolled, the mean age was 56.20 (±13.31) years and 261 were women, with a mean disease duration of 9.75 (±8.07) years. In the 12 months follow-up, 98/326 (30.1%) patients presented a disease flare. The concurrent presence of PD positive tenosynovitis and joint synovitis predicted disease flare, with an OR (95% CI) of 2.75 (1.45 to 5.20) in crude analyses and 2.09 (1.06 to 4.13) in adjusted analyses. US variables did not predict the worsening of function or radiographic progression. US was able to predict flare at 12 months but not at 6 months.ConclusionsPD positivity in tendons and joints is an independent risk factor of flare in patients with RA in clinical remission. Musculoskeletal ultrasound evaluation is a valuable tool to monitor and help decision making in patients with RA in clinical remission.


2016 ◽  
Vol 43 (11) ◽  
pp. 2010-2018 ◽  
Author(s):  
Jingjing Han ◽  
Yan Geng ◽  
Xuerong Deng ◽  
Zhuoli Zhang

Objective.Subclinical synovitis can be detected by ultrasound in patients with rheumatoid arthritis (RA) who are in clinical remission. We aimed to confirm its predictive value for flare and progressive bone erosion.Methods.A systematic literature search was performed in Pubmed, Web of Science, Embase, and Cochrane Library on September 7, 2014. Baseline clinical and ultrasonographic characteristics were collected. Methodological quality was assessed. Pooled OR were calculated using Mantel-Haenszel model. We explored the source of heterogeneity through subgroup analysis and completed a cumulative metaanalysis.Results.Thirteen articles were included (8 with flare, 4 with bone erosion, 1 with both flare and bone erosion). Metaanalysis revealed an association between power Doppler (PD) positivity and the risk of flare (OR 4.52, 95% CI 2.61–7.84, p < 0.00001, I2 = 21%), the risk of progressive bone erosion on patient level (OR 12.80, 95% CI 1.29–126.81, p = 0.03, I2 = 52%) and the risk of progressive bone erosion on joint level (OR 11.85, 95% CI 5.01–28.03, p < 0.00001, I2 = 0%). Further subgroup analysis showed a higher risk of flare in patients with a study period < 1 year (OR 19.98 vs 3.41). No significant differences were observed in the subgroup analysis in duration of remission, disease duration, and medications. Moreover, cumulative metaanalysis indicated the validation and an increasing accuracy of PD positivity in predicting flare since 2012.Conclusion.Ultrasound-detected subclinical synovitis can predict the risk of flare and progressive bone erosion in RA patients with clinical remission. Additionally, the flare of RA tends to occur within a followup of 1 year.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1120.2-1120
Author(s):  
E. Rojas ◽  
V. Valinotti ◽  
M. Vazquez ◽  
L. Roman ◽  
M. Maidana ◽  
...  

Background:Some studies prove that a significant percentage of patients with rheumatoid arthritis (RA) in sustained clinical remission has radiological progression or joint damage, and the presence of residual activity objectified by imaging studies such as ultrasonography could be related to a relapse or flare of RA.(1,2)Objectives:To determine the presence of subclinical synovitis measured by ultrasonography in patients with RA on sustained clinical remission from the Rheumatology service at Hospital de Clínicas, San Lorenzo, Paraguay.Materials and Methods:Prospective, cross sectional, descriptive study, in RA patients meeting ACR/EULAR 2010 criteria, older than 18 years, on sustained clinical remission (≥6 months), measured by ESR-DAS28 (<2,6), doing follow-ups on our service. A healthy control group was included. All groups signed informed consent. Synovial hypertrophy (SH) and intraarticular vascularization grades on Power Doppler (PD) mode were determined according to EULAR recommendations and OMERACT 7 group definitions. Clinical data were obtained from the service’s registries.SPSS 23rd version was used for data analysis. Quantitative variables were presented as means and qualitative as frequencies. Chi square test was performed for comparisons between dichotomous variables and t Student for continuous. For comparisons between variables the Spearman’s rank correlation coefficient was performed, and p≤0.05 for statistical significance. Factors predicting subclinical synovitis were analyzed with Odds Ratio (OR) CI 95%.Results:From 147 patients, 31 (21%) met remission criteria; 87.1% women, mean age 51.9±14.8 years. Mean disease duration was 9,06±10,81 years. 64,5% were RF and ACPA positive and 25,9% had erosions.Ultrasonograms were made in 20 joints of both hands: radiocarpals (RC), metacarpophalangeals (MCP) and proximal interphalangeals (PIP). 12 patients (38.7%) presented subclinical synovitis (SH≥2+PD), more frequently on RC (29% right, 22.6% left), and MCP (9.7% on 2RMCP, 9.7% 4LMCP). These patients had greater CDAI (3.9±1.37 vs 2.89±1.15, p=0.03), HAQ (0.14±0.29 vs 0.00±0.00, p=0.04), CRP (9.90±7.46 vs 4.74±2.30, p=0.00) RF levels (502.67±275.66 vs 200.92±158.43, p=0,00), greater prednisone (16.5% vs 3.2%, p=0.04), and methotrexate use (20.16±5.54 vs 17.50±3.98, p=0.01). None of the healthy controls presented subclinical synovitis.In binary logistic regression CRP levels, RF titers and methotrexate doses were associated to subclinical synovitis. This association is not found in multivariate logistic regression. Negative association was found between subclinical synovitis and two csDMARDs use.Conclusion:This is the first study of its type in Paraguayan patients, which clearly evidenced that an important part of RA patients in clinical remission still presented subclinical synovitis (HS≥2 + PD). It was associated with CRP, RF and methotrexate dose.References:[1]Płaza M, Nowakowska-Płaza A, Pracoń G, Sudoł-Szopińska I. Role of ultrasonography in the diagnosis of rheumatic diseases in light of ACR/EULAR guidelines. J Ultrason. marzo de 2016;16(64):55-64.[2]Foltz V, Gandjbakhch F, Etchepare F, Rosenberg C, Tanguy ML, Rozenberg S, et al. 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 & Rheumatism. 2012;64(1):67-76.Disclosure of Interests:None declared


2014 ◽  
Vol 41 (8) ◽  
pp. 1576-1582 ◽  
Author(s):  
Elena Ciubotariu ◽  
Cem Gabay ◽  
Axel Finckh

Objective.Randomized controlled studies have demonstrated protective advantages of biologic therapies over the synthetic disease-modifying antirheumatic drugs (DMARD) in slowing joint damage progression in patients with rheumatoid arthritis (RA). This effect appears to be largely independent of the clinical disease control. We measured the rate of radiographic progression in patients with RA in clinical remission treated with synthetic versus biologic DMARD.Methods.This is an observational cohort study of patients with RA in clinical remission, nested within the Swiss Clinical Quality Management in Rheumatoid Arthritis (SCQM-RA) Registry. The primary study outcome was the rate of radiographic progression (Ratingen erosion score), and a secondary outcome was functional disability [Health Assessment Questionnaire-Disability Index (HAQ-DI)] progression. We compared the rate of progression between synthetic and biologic DMARD using a multivariate regression model for longitudinal data, adjusting for potential confounders.Results.A total of 2055 patients in the SCQM-RA registry were in remission at least once from 1999 to 2012 and met the study inclusion criteria. Baseline characteristics of patients in remission receiving synthetic and biologic DMARD were not significantly different in terms of prognostic factors for joint damage progression. During followup, erosion progression differed significantly between the 2 groups [1.4% (95% CI: 1.1–1.6) vs 0.9% (95% CI: 0.5–1.2) of progression over 3 years, respectively, p < 0.001], with less damage progression in patients treated with biologic DMARD than with synthetic DMARD. This difference remained significant after adjusting for confounding factors. The evolution of the HAQ-DI score was also statistically better in the biologic group (p < 0.001).Conclusion.This observational study confirms that the rate of structural damage progression in clinical remission is decreased taking biologics compared to synthetic DMARD. However, while the difference is statistically significant it is probably not relevant from a clinical perspective.


2020 ◽  
Vol 16 (4) ◽  
pp. 267-279
Author(s):  
Mandana Khodashahi ◽  
Nayyereh Saadati ◽  
Maryam Sahebari ◽  
Zahra Rezaieyazdi ◽  
Neda Rastgou

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which is characterized by the hyperplasia of synovial tissue. Survivin is a member of the inhibitor of apoptosis protein family, which facilitates the formation of functional T-cell receptor and differentiation of memory T cells. Survivin plays an important role in the expression of major histocompatibility complex molecules and mature dendritic cells, which play the main role in the etiology of RA. This systematic review was conducted to investigate the evidence on the role of survivin as a diagnostic and predictive value in RA patients. All published articles related to the subject of interest and published up to 30 March 2018 were searched in three databases, including Google Scholar, PubMed, and Web of Science. After a detailed evaluation of the full-text version of the papers, 23 articles were entered into the study. The elevation of survivin in the preclinical phase of RA and its association with anti-cyclic citrullinated peptide (CCP) antibodies suggested it as a predictor of RA. Recently, survivin has been introduced as the biomarker of joint damage and poor response to antirheumatic treatment in RA patients. Based on the evidence, survivin level had high specificity and sensitivity in the diagnosis of RA patients. The results of the reviewed studies demonstrated that a positive survivin level was associated with the presence of anti-CCP antibodies.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 948-948
Author(s):  
I. Gessl ◽  
B. Wildner ◽  
P. Balint ◽  
M. A. D’agostino ◽  
P. Mandl

Background:The detection of damage in patients with rheumatoid arthritis (RA) is crucial for monitoring of therapy targets as well as for early diagnosis. Conventional radiography (CR) is commonly used to detect structural damage, in the form of bone erosions or loss of hyaline cartilage. Over the last years, musculoskeletal ultrasound (MSUS) was shown to be a sensitive and reliable method to detect erosion and cartilage loss as well as damage to soft tissue structures.Objectives:To identify and synthesize the evidence for the use and measurement properties of MSUS in assessing structural damage in patients with RA.Methods:A systematic literature search (SLR) of the PubMed, Embase and Cochrane Library was performed. Original articles were included that were published in English until 01/01/2019, reporting MSUS of bone erosion, cartilage loss or damage and tendon damage, and the measurement properties of MSUS according to the OMERACT Filter 2.1.Results:Of the 1.266 identified articles 79 were finally included, most of which reported on cross-sectional studies. The majority of the studies used the OMERACT definitions for ultrasonographic pathology. Among these, erosions were assessed in 72 (91.1%), cartilage damage in 12 (15.2%), tendons in 4 (5.1%) studies and enthesophytes in a single (1.3%) study. Erosions were rated by binary grading in 56 (77.8%) studies and by semiquantitative scoring in 27 (37.5%) studies. Global or sum scores were calculated in only 9 (12.5%) studies. Among 23 studies assessing erosions both by US and CR, only 1/23 (4.3%) study found a higher sensitivity of CR as compared to MSUS. Among studies assessing tendons, 3 (75%) used a semiquantitative score and one scored tendon rupture as being present or absent. Cartilage damage was graded in binary fashion, quantitatively by measuring cartilage thickness or semi-quantitatively. Hand joints were the most frequently evaluated joints (58, 73.4%). The overwhelming majority of studies assessed structural damage bilaterally (68, 86.1%), with 5 (6.3%) studies assessing only the dominant hand, 5 (6.3%) studies evaluating the clinically more affected side and 1 (1.3%) study assessing only the right hand. Validity, reliability and responsiveness were assessed in only 8 (10.1%), 10 (12.7%) and 4 (5.1%) studies respectively. Feasibility was not considered in any of the studies.Conclusion:While the results of this SLR suggest that US is a sensitive and feasible tool to detect damage in RA, they also highlight the need for further research and validation. Findings of this SLR will inform the next steps of the Working Group in developing an ultrasound score for assessing structural damage in patients with RA.Disclosure of Interests:None declared


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