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OBJECTIVES: The objectives of this study were (i) to evaluate the responsiveness of gout-specific US lesions representing urate deposition in patients receiving treat-to-target urate-lowering therapy using a binary and the OMERACT-defined semi-quantitative scoring systems; (ii) to determine the most responsive US measure for urate deposition and the optimal joint/tendon set for monitoring this. METHODS: US (28 joints, 14 tendons) was performed in microscopically verified gout patients initiating/increasing urate-lowering therapy and repeated after 6 and 12 months. Static images/videos of pathologies were stored and scored binarily and semi-quantitatively for tophus, double contour sign (DC) and aggregates. Lesion scores were calculated at patient level, as were combined crystal sum scores. Responsiveness of lesions-scored binarily and semi-quantitatively-was calculated at both patient and joint/tendon levels. RESULTS: Sixty-three patients underwent longitudinal evaluation. The static images/videos assessed retrospectively showed statistically significant decreases in tophus and DC, when scored binarily and semi-quantitatively, whereas aggregates were almost unchanged during follow-up. The responsiveness of the semi-quantitative tophus and DC sum scores were markedly higher than when using binary scoring. The most responsive measure for urate deposition was a combined semi-quantitative tophus-DC-sum score. A feasible joint/tendon set for monitoring included knee and first-second MTP joints and peroneus and distal patella tendons (all bilateral), representing the most prevalent and responsive sites. CONCLUSION: The OMERACT consensus-based semi-quantitative US gout scoring system showed longitudinal validity with both tophus and DC being highly responsive to treatment when assessed in static images/videos. A responsive US measure for urate deposition and a feasible joint/tendon set for monitoring were proposed and may prove valuable in future longitudinal studies.
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Artrite Gotosa , Gota , Humanos , Estudos Retrospectivos , Ácido Úrico , Gota/diagnóstico por imagem , Gota/tratamento farmacológico , Gota/patologia , UltrassonografiaRESUMO
OBJECTIVES: In a 2-year follow-up study of patients with axial spondyloarthritis (axSpA) in clinical remission who tapered TNF inhibitor (TNFi) treatment according to a clinical guideline, we aimed to investigate the proportion who successfully tapered/discontinued therapy and baseline predictors thereof. The proportion regaining clinical remission after flare and the progression on MRI/radiography were also assessed. METHODS: One-hundred-and-nine patients (78 [72%]/31 [28%] receiving standard and reduced dose, respectively) in clinical remission (BASDAI < 40, physician global score < 40) and no signs of disease activity the previous year tapered TNFi as follows: to two-thirds of standard dose at baseline, half at week 16, one-third at week 32 and discontinuation at week 48. Patients experiencing clinical, BASDAI or MRI flare (predefined criteria) stopped tapering and escalated to previous dose. Prediction analyses were performed by multivariable regression. RESULTS: One hundred and six patients (97%) completed 2 years' follow-up; 55 patients (52%) had successfully tapered: 23 (22%) receiving two-thirds, 15 (14%) half, 16 (15%) one-third dose and 1 (1%) discontinued. In patients at standard dose at baseline (n = 78), lower physician global score was the only independent predictor of successful tapering (odds ratio [OR] = 0.79 [95% CI: 0.64, 0.93]; P = 0.003). In the entire patient group lower physician global score (OR = 0.86 [0.75, 0.98]; P = 0.017), lower Spondyloarthritis Research Consortium of Canada (SPARCC) Sacroiliac Joint Erosion score (OR = 0.78 [0.57, 0.98]; P = 0.029) and current smoker (OR = 3.28 [1.15, 10.57]; P = 0.026) were independent predictors of successful tapering. At 2 years, 97% of patients were in clinical remission. Minimal changes in imaging findings were observed. CONCLUSION: After 2 years following a clinical guideline, 52% of patients with axSpA in clinical remission had successfully tapered TNFi, only 1% discontinued. Baseline physician global score was an independent predictor of successful tapering.
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Antirreumáticos , Espondiloartrite Axial , Espondilartrite , Antirreumáticos/uso terapêutico , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Espondilartrite/diagnóstico por imagem , Espondilartrite/tratamento farmacológico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
OBJECTIVES: To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating TNF inhibitor (TNFi) treatment. METHODS: Prospectively collected data on bio-naïve axSpA and PsA patients from routine care in 15 European countries were pooled. Three cohorts were defined according to year of TNFi initiation: A (1999-2008), B (2009-2014) and C (2015-2018). Retention, remission and response rates were assessed at 6, 12 and 24 months. RESULTS: In total, 27 149 axSpA and 17 446 PsA patients were included. Cohort A patients had longer disease duration compared with B and C. In axSpA, cohort A had the largest proportion of male and HLA-B27 positive patients. In PsA, baseline disease activity was highest in cohort A. Retention rates in axSpA/PsA were highest in cohort A and differed only slightly between B and C. For all cohorts, disease activity decreased markedly from 0 to 6 months. In axSpA, disease activity at 24 months was highest in cohort A, where also remission and response rates were lowest. In PsA, remission rates at 6 and 12 months tended to be lowest in cohort A. Response rates were at all time points comparable across cohorts, and less between-cohort disease activity differences were seen at 24 months. CONCLUSION: Our findings indicate that over the past decades, clinicians have implemented more aggressive treatment strategies in spondyloarthritis. This was illustrated by shorter disease duration at treatment initiation, decreased retention rates and higher remission rates during recent years.
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Artrite Psoriásica , Espondilartrite , Artrite Psoriásica/tratamento farmacológico , Estudos de Coortes , Humanos , Masculino , Espondilartrite/tratamento farmacológico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
OBJECTIVE: To evaluate ultrasound for diagnosing gout using consensus-based Outcome Measures in Rheumatology ultrasound definitions of gout lesions. METHODS: Ultrasound was performed in patients with clinically suspected gout. Joints (28) and tendons (26) were binarily evaluated for the Outcome Measures in Rheumatology gout lesions-double contour (DC), tophus, aggregates and erosions. Ultrasound assessment was compared with two reference standards: (i) presence of MSU crystals in joint/tophus aspirate (primary outcome) and (ii) ACR/EULAR 2015 gout classification criteria (secondary outcome). Both reference standards were evaluated by rheumatologists blinded to ultrasound findings. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of each ultrasound lesion against both reference standards were determined. RESULTS: Eighty-two patients (70 men), mean age 62.4 (range 19-88) years, were included. Fifty-seven patients were MSU-positive whereas 25 patients were MSU-negative (no MSU crystals: 23; aspiration unsuccessful: 2). Of these 25 patients, three patients were classified as ACR/EULAR-positive (i.e. totally 60 ACR/EULAR-positive patients). All ultrasound lesions had high sensitivities for gout (0.77-0.95). DC and tophus showed high specificities (0.88-0.95), positive predictive values (0.94-0.98) and accuracies (0.82-0.84) when both reference standards were used. In contrast, low specificities were found for aggregates and erosions (0.32-0.59). Ultrasound of MTP joints for DC or tophus, knee joint for DC and peroneus tendons for tophus was sufficient to identify all MSU-positive patients with ultrasound signs of gout at any location. CONCLUSION: Ultrasound-visualized DC and tophus, as defined by the Outcome Measures in Rheumatology ultrasound group, show high specificities, positive predictive values and accuracies for diagnosing gout and are therefore valid tools in clinical practice.
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Gota/diagnóstico por imagem , Avaliação de Resultados em Cuidados de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Articulações/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Sistema Musculoesquelético/química , Valor Preditivo dos Testes , Padrões de Referência , Reumatologia , Sensibilidade e Especificidade , Tendões/diagnóstico por imagem , Ultrassonografia , Ácido Úrico/análise , Adulto JovemRESUMO
The use of ultrasonography has a considerable potential for diagnosis and monitoring of gout due to its capacity to detect urate crystal deposits in joints, e.g. on the cartilage surface, visualised as the double contour sign, and in soft tissues, e.g. as tophi. Furthermore, ultrasonography can visualise both synovitis and bone erosion. Consensus-based definitions for ultrasonographic elementary lesions in gout were validated in 2015, and ultrasonography is already included in the 2015 ACR/EULAR classification criteria for gout. This report evaluates the current literature on the use of ultrasonography for diagnosing and monitoring gout.
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Gota/diagnóstico por imagem , Articulações/diagnóstico por imagem , Reumatologia/métodos , Ultrassonografia/métodos , Gota/fisiopatologia , Gota/terapia , Humanos , Articulações/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe. METHODS: Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0-10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.3 after 6/12/24 months of secukinumab treatment were calculated.Remission and drug retention rates in r-axSpA versus nr-axSpA patients were compared by logistic and Cox regression models (unadjusted/adjusted for age+sex/adjusted for multiple confounders). RESULTS: Overall, 1161 secukinumab-treated patients were included (r-axSpA/nr-axSpA: 922/239). At baseline, r-axSpA patients had longer disease duration and higher C reactive protein, were more often male and HLA-B27 positive and had received fewer prior biological or targeted synthetic disease-modifying antirheumatic drugs compared with nr-axSpA patients, whereas PROs were largely similar.During follow-up, crude PRO remission rates were significantly higher in r-axSpA compared with nr-axSpA patients (6 months: pain≤2: 40%/28%, OR=1.7; BASDAI≤2: 37%/25%, OR=1.8), as were drug retention rates (24 months: 66%/58%, HR 0.73 (ref: r-axSpA)). Proportions of patients achieving ASDAS ID were low for both groups, particularly nr-axSpA (6 months: 11%/8%).However, when adjusting for age+sex, these differences diminished, and after adjusting for multiple confounders, no significant between-group differences remained for either remission or drug retention rates. CONCLUSION: Crude remission/drug retention rates in European secukinumab-treated patients were higher in r-axSpA compared with nr-axSpA patients. In adjusted analyses, secukinumab effectiveness was similar in both groups, suggesting that observed differences were related to factors other than radiographic status.
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Anticorpos Monoclonais Humanizados , Espondiloartrite Axial , Humanos , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Adulto , Resultado do Tratamento , Europa (Continente) , Pessoa de Meia-Idade , Espondiloartrite Axial/tratamento farmacológico , Espondiloartrite Axial/etiologia , Antirreumáticos/uso terapêutico , Estudos Prospectivos , Índice de Gravidade de Doença , Medidas de Resultados Relatados pelo Paciente , Radiografia , Indução de RemissãoRESUMO
OBJECTIVES: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates. PATIENTS AND METHODS: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0-10) and Health Assessment Questionnaire (HAQ) ≤0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan-Meier plots with log-rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates. RESULTS: We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24-month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84-1.02]). CONCLUSION: In this large European real-world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders.
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Anticorpos Monoclonais Humanizados , Artrite Psoriásica , Espondiloartrite Axial , Humanos , Artrite Psoriásica/tratamento farmacológico , Resultado do Tratamento , DorRESUMO
BACKGROUND: The Calcium Pyrophosphate Deposition (CPPD) subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound working group was established to validate ultrasound as an outcome measure instrument for CPPD, and in 2017 has developed and validated standardised definitions for elementary lesions for the detection of calcium pyrophosphate crystals in joints. The aim of this study was to develop and evaluate the reliability of a consensus-based ultrasound scoring system for CPPD extent, representing the next phase in the OMERACT methodology. METHODS: In this study the novel scoring system for CPPD was developed through a stepwise process, following an established OMERACT ultrasound methodology. Following a previous systematic review to gather available evidence on existing scoring systems for CPPD, the novel scoring system was developed through a Delphi survey based on the expert opinion of the members of the OMERACT Ultrasound working group-CPPD subgroup. The reliability of the scoring system was then tested on a web-based and patient-based exercise. Intra-reader and inter-reader reliability of the new scoring system was assessed using weighted Light's κ coefficients. FINDINGS: The four-grade semiquantitative scoring system consisted of: grade 0 (no findings consistent with CPPD), grade 1 (≤3 single spots or 1 small deposit), grade 2 (>3 single spots or >1 small deposit or ≥1 larger deposit occupying ≤50% of the structure under examination in the reference image-ie, the scanning view with the highest grade of depositions), and grade 3 (deposits that occupy more than 50% of the structure under examination in the reference image). The score should be applied to the knee (menisci and hyaline cartilage) and the triangular fibrocartilage complex of the wrist. The intra-reader and inter-reader reliabilities on static images were almost perfect (κ 0·90 [95% CI 0·79-1·00] and κ 0·84 [0·79-0·88]), and on the eight patients recruited (four [50%] female and four [50%] male) were substantial (κ 0·72 [95% CI 0·47 to 0·96] and 0·66 [0·61 to 0·71]). INTERPRETATION: This OMERACT ultrasound scoring system for CPPD was reliable on both static images and patients. The scoring system might be a valuable tool for ensuring valid and comparable results in clinical trials and could help monitor the extent of crystal deposition in patients with CPPD in clinical practice. FUNDING: The Italian Ministry of Health - Ricerca Corrente.
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Calcinose , Pirofosfato de Cálcio , Humanos , Feminino , Masculino , Reprodutibilidade dos Testes , Difosfatos , UltrassonografiaRESUMO
OBJECTIVE: This study aimed to develop (1) a new ultrasound definition for aggregates and (2) a semi-quantitative ultrasound scoring system (0-3) for tophus, double contour and aggregates. Furthermore, the intra- and inter-reader reliabilities of both the re-defined aggregates and the semi-quantitative scoring system were assessed using static image exercises. METHODS: Thirty-seven rheumatologists were invited. A Delphi process was used for re-defining aggregates and for selecting a semi-quantitative scoring system with >75% agreement obligate for reaching consensus. Subsequently, a web-based exercise on static ultrasound images was conducted in order to assess the reliability of both the re-defined aggregates and the semi-quantitative scoring system. RESULTS: Twenty rheumatologists contributed to all rounds of the Delphi and image exercises. A consensual re-definition of aggregates was obtained after three Delphi rounds but needed an overarching principle for scoring aggregates in patients. A consensus-based semi-quantitative ultrasound scoring system for gout lesions was developed after two Delphi rounds. The re-definition of aggregates showed good intra- and inter-reader reliability (κ-values 0.71 and 0.61). The reliabilities of the scoring system were good for all lesions with slightly higher intra-reader (κ-values 0.74-0.80) than inter-reader reliabilities (κ-values 0.61-0.67). CONCLUSION: A re-definition of aggregates was obtained with a good reliability when assessing static images. The first consensus-based semi-quantitative ultrasound scoring system for gout-specific lesions was developed with good inter- and intra-reader reliability for all lesions when tested in static images. The next step is to assess the reliabilities when scoring lesions in patients.
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Gota , Consenso , Exercício Físico , Gota/diagnóstico por imagem , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , UltrassonografiaRESUMO
OBJECTIVES: To evaluate the sensitivity to change of ultrasound structural gout lesions, as defined by the Outcome Measures in Rheumatology (OMERACT) ultrasound group, in patients with gout during urate-lowering therapy (ULT). METHODS: Ultrasound (28 joints, 26 tendons) was performed in patients with microscopically verified gout initiating or increasing ULT and repeated after 3 and 6 months. Joints and tendons were evaluated by ultrasound for presence of the OMERACT structural gout lesions-double contour sign (DC), tophus, aggregates and erosion-scored binarily. A sum score was calculated at patient and lesion level. Changes at 3 and 6 months in patient sum scores and lesion scores at different locations were evaluated. RESULTS: 50 patients (48 men), mean age 68.9 (range, 30-88) years, were included. Ultrasound showed a statistically significant decrease in DC and tophus sum scores from 0 months (3.16 and 2.68, respectively) to 3 months (2.33 and 2.43) and 6 months (1.34 and 1.83) (all p<0.002). The aggregate sum score only decreased significantly from 3 to 6 months (6.02 to 5.02, p=0.002), whereas erosion sum score remained almost unchanged. All four structural lesions were most commonly found in metatarsophalangeal (MTP) 1 joints (>1 lesions bilaterally), and furthermore MTP2-4 and knee joints were common sites especially for DC. Likewise, these regions were the locations with most pronounced changes in scores. CONCLUSION: Ultrasound assessment of the OMERACT structural gout lesions scored binarily seems to be a useful tool for monitoring urate depositions during ULT. Particularly DC and tophus showed sensitivity to change after only 3 months of treatment.
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Gota/diagnóstico por imagem , Avaliação de Resultados em Cuidados de Saúde , Ultrassonografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Articulações/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sistema Musculoesquelético/química , Valor Preditivo dos Testes , Estudos Prospectivos , Tendões/diagnóstico por imagem , Ácido Úrico/análiseRESUMO
BACKGROUND: Dual-energy CT (DECT) can acknowledge differences in tissue compositions and can colour-code tissues with specific features including monosodium urate (MSU) crystals. However, when evaluating gout patients, DECT frequently colour-codes material not truly representing MSU crystals and this might lead to misinterpretations. The characteristics of and variations in properties of colour-coded DECT lesions in gout patients have not yet been systematically investigated. The objective of this study was to evaluate the properties and locations of colour-coded DECT lesions in gout patients. METHODS: DECT of the hands, knees and feet were performed in patients with suspected gout using factory default gout settings, and colour-coded DECT lesions were registered. For each lesion, properties [mean density (mean of Hounsfield Units (HU) at 80 kV and Sn150kV), mean DECT ratio and size] and location were determined. Subgroup analysis was performed post hoc evaluating differences in locations of lesions when divided into definite MSU depositions and possibly other lesions. RESULTS: In total, 4033 lesions were registered in 27 patients (23 gout patients, 3918 lesions; 4 non-gout patients, 115 lesions). In gout patients, lesions had a median density of 160.6 HU and median size of 6 voxels, and DECT ratios showed an approximated normal distribution (mean 1.06, SD 0.10), but with a right heavy tail consistent with the presence of smaller amounts of high effective atomic number lesions (e.g. calcium-containing lesions). The most common locations of lesions were 1st metatarsophalangeal (MTP1), knee and midtarsal joints along with quadriceps and patella tendons. Subgroup analyses showed that definite MSU depositions (large volume, low DECT ratio, high density) had a similar distribution pattern, whereas possible calcium-containing material (high DECT ratio) and non-gout MSU-imitating lesions (properties as definite MSU depositions in non-gout patients) were primarily found in some larger joints (knee, midtarsal and talocrural) and tendons (Achilles and quadriceps). MTP1 joints and patella tendons showed only definite MSU depositions. CONCLUSION: Colour-coded DECT lesions in gout patients showed heterogeneity in properties and distribution. MTP1 joints and patella tendons exclusively showed definite MSU depositions. Hence, a sole focus on these regions in the evaluation of gout patients may improve the specificity of DECT scans.
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Gota , Ácido Úrico , Cor , Gota/diagnóstico por imagem , Humanos , Tendões , Tomografia Computadorizada por Raios XRESUMO
Psoriatic arthritis (PsA) is an inflammatory joint disease characterised by the presence of arthritis and often enthesitis and/or spondylitis in patients with psoriasis. However, it presents a wide range of disease manifestations in various patterns. Imaging is an important part of management of PsA, and is used for multiple reasons including establishing/confirming a diagnosis of inflammatory joint disease, determining the extent of disease, monitoring activity and damage, assessing therapeutic efficacy, and identifying complications of disease or treatment, in the setting of clinical practice or clinical studies. Magnetic resonance imaging (MRI) allows detailed assessment of all peripheral and axial joints involved in PsA, and can visualise both inflammation and structural changes. Ultrasonography (US) can visualise many of the peripheral heterogeneous tissue compartments affected by PsA. In contrast to MRI, US is not useful for assessing axial involvement in the spine and sacroiliac joints. In this paper, we will provide an overview of the status, strengths and limitations of MRI and US in peripheral PsA in routine clinical practice and clinical trials.