Musculoskeletal ultrasound using superb microvascular imaging documents treatment response to biosimilar infliximab in rheumatoid arthritis

2021 ◽  
Vol 14 (2) ◽  
pp. e239112
Author(s):  
Julian Alejandro Santos ◽  
Cherica Afurong Tee ◽  
Romelito Jose Galvan Galsim ◽  
Michael Lucas Tee

A 60-year-old woman with rheumatoid arthritis consulted for acute flare. She had elevated disease activity score 28 - erythrocyte sedimentation rate (DAS 28-ESR) of 6.88 and clinical disease activity index (CDAI) of 32. Her 12-joint ultrasound revealed widespread joint effusion. Synovial vascularity scores measured through superb microvascular imaging (SMI) and power Doppler were universally increased. We documented her treatment response 2 weeks after she received a single dose of biosimilar infliximab using clinical and sonographic data. Her DAS 28-ESR and CDAI scores decreased to 4.21 and 7.0, respectively. Reduction in synovial vascularity scores was demonstrated using SMI. While there was near total resolution in joint effusion and tenosynovitis, SMI was able to demonstrate synovial vascularity in joints with no clinical swelling nor tenderness. Musculoskeletal ultrasound and superb microvascular imaging are useful adjuncts in evaluating synovitis in rheumatoid arthritis and documenting treatment response through documentation of synovial vascularity, effusion and tenosynovitis.

2017 ◽  
Vol 76 (12) ◽  
pp. 2031-2037 ◽  
Author(s):  
Maria Karolina Jonsson ◽  
Nina Paulshus Sundlisæter ◽  
Hilde Haugedal Nordal ◽  
Hilde Berner Hammer ◽  
Anna-Birgitte Aga ◽  
...  

ObjectivesCalprotectin is an inflammatory marker of interest in rheumatoid arthritis (RA). We evaluated whether the level of calprotectin was associated with disease activity, and if it was predictive of treatment response and radiographic progression in patients with early RA.MethodsPlasma from disease-modifying antirheumatic drug (DMARD)-naïve patients with RA fulfilling 2010 American College of Rheumatology/European League Against Rheumatism classification criteria with symptom duration <2 years was analysed for calprotectin at baseline, and after 1, 3 and 12 months. All patients received treat-to-target therapy, as part of a randomised controlled strategy trial (ARCTIC). The association between calprotectin, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) and measures of disease activity were assessed by correlations. We used likelihood ratios and logistic regression models to assess the predictive value of the baseline inflammatory markers for treatment response and radiographic damage.Results215 patients were included: 61% female, 82% anti-citrullinated peptide antibody positive, mean (SD) age 50.9 (13.7) years and median (25, 75 percentile) symptom duration 5.8 (2.8, 10.5) months. Calprotectin was significantly correlated with Clinical Disease Activity Index (r=0.32), ESR (r=0.50) and ultrasonography power Doppler (r=0.42) before treatment onset. After 12 months of treatment, calprotectin, but not ESR and CRP, was significantly correlated with power Doppler (r=0.27). Baseline levels of calprotectin, ESR and CRP were not predictive of treatment response, but high levels of calprotectin were associated with radiographic progression in multivariate models.ConclusionsCalprotectin was correlated with inflammation assessed by ultrasound before and during DMARD treatment, and was also associated with radiographic progression. The data support that calprotectin may be of interest as an inflammatory marker when assessing disease activity in different stages of RA.Trial registration numberNCT01205854; Post-results.


Author(s):  
Sahar A. Ahmed ◽  
Enas M. Darwish ◽  
Walaa A. Attya ◽  
Mai Samir ◽  
Mennatallah Elsayed ◽  
...  

Background: Rheumatoid arthritis (RA) is a common progressive chronic inflammatory autoimmune disease which affects mostly small joints, causing pain, swelling, deformity, and disability. Although progress has been made in exploring RA nature, still there is a lot to know about the disease pathogenesis, diagnosis, and treatment. Aim of the Work: To investigate the role of serum anti-carbamylated protein antibodies and 14-3-3η in the diagnosis of RA compared to rheumatoid factor (RF), anti-CCP antibodies, and highfrequency musculoskeletal ultrasound used to assess the disease activity and joint damage. Methods: Serum anti-carbamylated protein antibodies and 14-3-3η were measured using ELISA in 61 RA patients and 26 normal controls. RA Disease Activity Score (DAS 28), X-ray and musculoskeletal ultrasound (hands and feet), carotid ultrasound (Intima-Media Thickness IMT) were used in assessing the RA disease. Results: Anti-carbamylated protein antibodies were significantly elevated in RA patients 4.5 (4.1- 8.9 U⁄ml) compared to the control 3.2(1.9- 4.3 U⁄ml) (p< 0.001) but 14-3-3η showed no significant difference. There was a significant positive correlation between anti-carbamylated protein antibodies, 14-3-3η levels and disease activity score assessed by DAS 28, increased IMT measured by carotid duplex, total synovitis and total erosion score were assessed by musculoskeletal ultrasound. There was no correlation between RF and anti-CCP antibodies. Anti-carbamylated protein antibodies were found to have 66.7% sensitivity and 85.2% specificity in RA diagnosis, while 14- 3-3η had 51.9% sensitivity and 72.1% specificity. Conclusion: Anti-carbamylated protein antibodies and 14-3-3η have a high sensitivity and specificity in RA diagnosis and had a correlation with the disease activity and joint damage.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 553.1-553
Author(s):  
K. Janke ◽  
K. Biester ◽  
D. Krause ◽  
B. Richter ◽  
C. Schürmann ◽  
...  

Background:Biologics for the treatment of rheumatoid arthritis (RA) have different modes of action to target auto-inflammatory processes causing the signs and symptoms of the disease. Different biologics may thus have different effects on inflammatory markers. For instance, previous studies have shown that the interleukin-6-inhibitor tocilizumab (TOC) decreases the level of acute phase reactants (APRs) [1]. Such direct effects on inflammatory markers may lead to an overestimation of clinical response if disease activity is measured via scores including inflammatory markers, such as the Disease Activity Score 28 (DAS 28). The detected changes in disease activity may not adequately reflect the clinical improvement of signs and symptoms.Objectives:In our study, we compared biologics with each other using two different disease activity scores: the DAS 28 including APRs and the clinical disease activity index (CDAI) excluding APRs. The aim of this study was to assess whether the use of the two different scores affects comparative effectiveness studies on biologics for the treatment of RA.Methods:We compared results on the comparative effectiveness of biologics using the corresponding thresholds for low disease activity (LDA) for the DAS 28 (< 3.2) and the CDAI (≤ 10). We performed two separate network meta-analyses (NMAs) after a thorough step-by-step evaluation of the similarity, homogeneity and consistency assumptions of the patient populations and the study data.Our study formed part of a systematic review (including NMAs) that was largely based on clinical study reports and re-analyses of LDA using individual patient data provided by sponsors for studies conducted up to 2017. Thus, the analyses include hitherto unknown data on LDA analysed by means of the CDAI, especially data from older studies. An extensive comparison of DAS 28 and CDAI in different patient populations was possible.Results:For all analysed patient populations, comparisons of TOC versus other biologics yielded remarkable results: advantages for TOC were found in NMAs using the DAS 28, which were not confirmed in NMAs using the CDAI. For methotrexate (MTX)-naïve patients, using the DAS 28, TOC showed a greater benefit than abatacept (ABA), certolizumab pegol (CZP), and etanercept (ETA), which was not confirmed by the CDAI. In contrast, TOC showed less benefit than adalimumab (ADA) and ETA. For patients after MTX failure and using the DAS 28, TOC showed a greater benefit than ABA, ADA, anakinra (ANA), ETA, golimumab (GOL), and infliximab (INF). With the exception of ANA, these advantages were not confirmed by the CDAI. Similar differences between DAS 28 and CDAI were shown in patients treated with biologics in monotherapy or after failure of biologics.Conclusion:In comparative effectiveness studies of biologics, the assessment of LDA using the DAS 28 instead of the CDAI leads to a consistent overestimation of the benefit of TOC in all patient populations, regardless of pre-treatment or combined therapy with MTX. The inclusion of APRs in disease activity scores may thus introduce bias. A score excluding inflammatory markers should therefore be used to ensure valid results.References:[1]Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum 2011; 63(1): 43-52.Disclosure of Interests:Kirsten Janke: None declared, Katharina Biester: None declared, Dietmar Krause Grant/research support from: Pfizer and AbbVie (Abbott), Bernd Richter: None declared, Christoph Schürmann: None declared, Katharina Hirsch: None declared, Beate Wieseler: None declared


2018 ◽  
Vol 77 (10) ◽  
pp. 1421-1425 ◽  
Author(s):  
Nina Paulshus Sundlisæter ◽  
Anna-Birgitte Aga ◽  
Inge Christoffer Olsen ◽  
Hilde Berner Hammer ◽  
Till Uhlig ◽  
...  

ObjectiveTo explore associations between remission, based on clinical and ultrasound definitions, and future good radiographic and physical outcome in early rheumatoid arthritis (RA).MethodsNewly diagnosed patients with RA followed a treat-to-target strategy incorporating ultrasound information in the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen (ARCTIC) trial. We defined 6-month remission according to Disease Activity Score, Disease Activity Score in 28 joints-erythrocyte sedimentation rate, American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean criteria, Simplified Disease Activity Index, Clinical Disease Activity Index and two ultrasound definitions (no power Doppler signal, grey scale score ≤2). Two outcomes were defined: no radiographic progression and good outcome (no radiographic progression+physical function≥general population median), both sustained 12–24 months. We calculated the ORs of these outcomes for the remission definitions.ResultsOf 103 patients, 42%–82% reached remission at 6 months, dependent on definition. Seventy-one per cent of patients had no radiographic progression and 37% had good outcome. An association between 6-month remission and no radiographic progression was observed for ACR/EULAR Boolean remission (44 joints, OR 3.2, 95% CI 1.2 to 8.4), ultrasound power Doppler (OR 3.6, 95% CI 1.3 to 10.0) and grey scale remission (OR 3.2, 95% CI 1.2 to 8.0). All clinical, but not ultrasound remission criteria were associated with achievement of a good outcome.ConclusionsOur data support ACR/EULAR Boolean remission based on 44 joints as the preferred treatment target in early RA. Absence of ultrasound inflammation was associated with no radiographic progression.Trial registration numberNCT01205854; Post-results.


2021 ◽  
Author(s):  
Harpreet Singh ◽  
Somdatta Giri ◽  
Hemant Kumar ◽  
Pratibha Yonzone ◽  
Mahima Khatkar

Abstract Objective To assess the utility of Patient Based Disease Activity Score 2 (PDAS 2) in assessing the disease activity in Rheumatoid arthritis (RA). Methods A prospective cohort study was conducted on 80 patients of RA. The demographic and clinical characteristics of the patients were recorded. They were assessed for disease activity using “Disease Activity Score 28” (DAS 28), “Clinical Disease Activity Index” (CDAI) and PDAS 2 score at baseline (M0), at 2 months (M2) and at 4 months(M4) while they were on treatment. Data was analyzed for correlation of PDAS-2 with other scores and internal reliability. P < 0.05 was considered for statistical significance. Results The mean age was 40.13\(\pm\) 11.74 years with 70 females and 10 males. There was significant reduction in DAS28, CDAI and PDAS 2 score over 4 month follow up (all scores’ p values < 0.001). Internal reliability (as assessed by Cronbach’s Alpha) of PDAS 2 was 0.578. PDAS 2 showed significant correlation with DAS28 at M0, M2 and M4 (r = 0.792, 0.757 and 0.669 respectively, p value < 0.001) and CDAI (r = 0.861, 0.832 and 0.695 respectively, p value < 0.001). Overall there was a significant agreement between DAS 28 and PDAS 2 (K = 0.788,p < 0.001) and between CDAI and PDAS 2 (K = 0.766,p < 0.001). Conclusion PDAS-2 score can be routinely used in the clinical practice owing to its correlation with DAS-28/CDAI and because of the advantage that it assessed the patients’ daily living activities.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Sanchaita Misra ◽  
Sumantro Mondal ◽  
Sudipta Chatterjee ◽  
Aharna Guin ◽  
Pradyot Sinhamahapatra ◽  
...  

Objective. Upregulation of various proinflammatory and angiogenic mediators orchestrates the typical pathological synovial alterations in rheumatoid arthritis (RA). DAS28-CRP is commonly used for assessment of RA disease activity and power Doppler ultrasonography (PDUS) is an important modality for assessing synovial vascularity. This study was intended to look for the association of various inflammatory and angiogenic mediators, with respect to different PDUS vascularity grades and disease activity status, in early RA patients. Methods. 50 early RA patients (<6 months disease duration) with either moderate or high disease activity and 30 healthy controls were included in this study. RA patients were subcategorized based on PDUS vascularity grading of wrist joints. Serum levels of proinflammatory cytokines [tumor necrosis factor-α (TNF- α); interleukin-6(IL-6)] and angiogenic markers [angiopoietin-1 and 2 (Ang-1 and Ang-2); vascular endothelial growth factor (VEGF) ] were measured and compared among different patient subgroups. Results. Among 50 patients, 22 and 28 patients had moderate and high DAS28-CRP score, respectively. Patients with grade 3 PDUS score, even with moderate DAS value, showed a significant rise in Ang-1 (p<0.02), VEGF (p<0.008), Ang-2 (p <0.001), and TNF-α (p<0.005) level compared to grade 2 PDUS patients with high DAS values. Conclusion. Higher serum level of angiogenic and inflammatory markers was noted among patients with moderate disease activity but with advanced PDUS vascularity (grade 3) in comparison to high disease activity group with less severe PDUS vascularity (grade 2). PDUS vascularity grading better reflects some markers of angiogenesis and inflammation, than composite disease activity index.


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Charles Raine ◽  
Jessica Manson ◽  
Coziana Ciurtin ◽  
Ian Giles

Abstract Background The utility of musculoskeletal ultrasound (MSK-US) in the measurement of disease activity of rheumatoid arthritis (RA) is well established. However, it has not been formally studied in pregnancy, with the literature limited to a single case report. Standard disease activity assessment in RA pregnancy comprises measurement of the DAS28(3) CRP score, which removes the visual analogue score (VAS) and replaces ESR with CRP, as both of these components may be confounded by pregnancy. Use of this modified score remains problematic as the tender joint count may be affected by non-specific musculoskeletal pain in pregnancy, and the swollen joint count may be obscured by peripheral oedema, especially late in pregnancy. No study of RA in pregnancy has used MSK-US to measure disease activity. Our objective was to conduct a pilot study of MSK-US in RA pregnancy, and compare findings with clinical assessment using the DAS28(3)CRP score. Methods We offered MSK-US to pregnant RA patients attending the UCLH obstetric rheumatology clinic from September 2018 to September 2019. Patients were assessed longitudinally through pregnancy/post-partum where possible. Examination was undertaken using a Logiq S8 US machine. The standard protocol comprised 22-joint assessment of hands (dorsal longitudinal and transverse views of wrists, metacarpophalangeal and proximal interphalangeal joints). In the feet, bilateral MTP joints were scanned with longitudinal views. Quantification of Power Doppler (PD) signal and grey scale (GS) synovitis was made as per the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) US definitions. PD and GS scores were calculated as mean scores of all joints scanned. Results To date, 17 pregnant RA patients have undergone a total of 35 MSK-US studies. Disease activity assessments showed 10/17 patients with persistent low activity through pregnancy, 5/17 with moderate or good response, 1/17 with no response and 1/17 with a moderate flare. Overall, PD scores correlated well with DAS28(3) CRP assessment (R2 = 0.68). All patients at moderate or high disease activity by DAS28(3) CRP had ≥1 joint with detectable PD signal, but 2/21 patients clinically in ‘remission’ and 3/7 patients in ‘low disease activity’ had detectable PD. One patient with only 2 tender and 1 swollen joints (and normal CRP; DAS28 3.17) had very extensive PD signal and contributed to the decision to recommence anti-TNF treatment in the 3rd trimester. It was noted that increased vascularity in pregnancy can complicate the assessment of synovial PD signal. MSK-US was particularly helpful in distinguishing true joint synovitis from subcutaneous oedema in the feet. Conclusion This is the first series of MSK-US in pregnant RA patients. The detection of active joint synovitis (by PD signal) in clinical remission/low disease activity states suggests a potential role for MSK-US in confirming apparent low disease activity in pregnancy, and thus guiding stratification of treatment. Disclosures C. Raine None. J. Manson None. C. Ciurtin None. I. Giles None.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Charles Raine ◽  
Jessica Manson ◽  
Coziana Ciurtin ◽  
Ian Giles

Abstract Background/Aims  In rheumatoid arthritis (RA), musculoskeletal ultrasound (MSK-US) has greater sensitivity for the detection of active disease than clinical assessment using the DAS28 score, which is prone to false elevation by a spuriously high tender joint count (TJC) and/or visual analogue score (VAS) from non-RA causes. Thus, DAS28 may correlate poorly with MSK-US findings. In pregnancy, standardised disease activity of RA comprises calculation of the modified DAS28(3)CRP score, with removal of the VAS and ESR, both of which are confounded by pregnancy, and replacement with CRP; however, it is unknown whether non-specific musculoskeletal pain and/or peripheral oedema in (especially late) pregnancy might contribute to the TJC or swollen joint count (SJC) respectively and thus render this adapted score less reliable. Therefore, we conducted this study of pregnant RA patients and controls to assess the ability of the DAS28(3)CRP to detect disease activity compared with MSK-US. Methods  Pregnant RA patients were recruited from the UCLH obstetric rheumatology clinic from September 2018 to March 2020. Patients underwent clinical assessment with DAS28(3)CRP and MSK-US longitudinally through pregnancy/post-partum. A control group of age-matched non-pregnant female RA patients was recruited from general rheumatology clinics and had equivalent assessments. MSK-US was undertaken using a Logiq S8. The standard protocol comprised 22-joint assessment of hands (dorsal longitudinal and transverse views of wrists, metacarpophalangeal and proximal interphalangeal joints). Quantification of Power Doppler (PD) signal was made as per the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) US definitions. PD scores were calculated as mean scores of all joints scanned. Statistical correlations were performed in SPSS using Spearman’s rank coefficient as data were non-normally distributed. Results  A total of 45 MSK-US scans of pregnant/postpartum RA patients (N = 24, mean age 34.5+-3.6) were performed and compared to a control group of non-pregnant RA patients, who were scanned once each (N = 18, mean age 32.3+-5.2; p = 0.12). In the second (T2) and third trimester (T3) and the postpartum (PP), there was a significant positive correlation between DAS28(3)CRP and PD score (T2, ρ = 0.87 (p &lt; 0.01); T3, ρ = 0.76 (p &lt; 0.01); PP, ρ = 0.68 (p = 0.03)). Interestingly, each of these were stronger correlations than the equivalent comparison in non-pregnant RA patients (ρ = 0.51 (p = 0.03)). TJC also significantly positively correlated with PD score in each trimester of pregnancy and postpartum, but not in non-pregnant patients; difference between correlation coefficients was statistically significant for each trimester (T1, p &lt; 0.01; T2, p = 0.05; T3, p = 0.05). Conclusion  Interestingly, we found that that DAS28(3)CRP correlates better with PD signal on MSK-US in pregnancy than in non-pregnancy. Specifically, there was significantly better correlation of the TJC with PD score. It is unclear why non-inflammatory contributors to the TJC may be less prominent in pregnancy and further investigation is warranted. Disclosure  C. Raine: Grants/research support; C.R. has received research funding from UCB. J. Manson: None. C. Ciurtin: None. I. Giles: Grants/research support; IG has received an unrestricted educational grant, speaker's fees and travel fees from UCB.


2017 ◽  
Vol 45 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Leslie R. Harrold ◽  
Heather J. Litman ◽  
Sean E. Connolly ◽  
Sheila Kelly ◽  
Winnie Hua ◽  
...  

Objective.Assess whether baseline anticyclic citrullinated peptide antibodies (anti-CCP) status is associated with treatment response in patients with rheumatoid arthritis (RA) initiating abatacept (ABA) or a tumor necrosis factor-α inhibitor (TNFi).Methods.Using the Corrona RA registry, patients were identified who initiated ABA or a TNFi (June 2004–January 2015), had a followup visit 6 months (± 3 mos) after initiation, and anti-CCP measured at or prior to initiation. Primary outcome was mean change in Clinical Disease Activity Index (CDAI) from initiation to 6 months. Treatment response was evaluated based on a typical patient profile (female, aged 57 yrs, body mass index of 30 kg/m2, baseline CDAI of 20, 1 prior biologic, and no comorbidities other than RA). Secondary outcomes included remission and low disease activity.Results.There were 566 ABA initiators [anti-CCP+ (≥ 20 units/ml): n = 362; anti-CCP− (< 20 units/ml): n = 204] and 1715 TNFi initiators (anti-CCP+: n = 1113; anti-CCP−: n = 602). Differences between treatment groups included baseline disease duration, CDAI, and prior biologic use. At 6 months, anti-CCP+ ABA initiators were associated with significantly greater CDAI response versus anti-CCP− ABA initiators; no significant difference was observed for TNFi initiators. When considering a typical RA patient profile, CDAI response was greater in anti-CCP+ versus anti-CCP− ABA initiators; anti-CCP+ versus anti-CCP− TNFi initiators were similar. Secondary outcome responses were also greater in anti-CCP+ versus anti-CCP− ABA initiators; TNFi initiators did not differ by anti-CCP status.Conclusion.In a US-based clinical practice setting, anti-CCP status was associated with a differential treatment response to ABA, but not TNFi.


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