Search

Objective: To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA. Methods: Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3 months and hands and feet radiographs every 6 months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed. Results: A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [β(95% CI): 0.11 (− 0.16;0.39)] assessed at various intervals up to 12 months later. Conclusion: Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of body mass index (BMI) with pain in people with hand osteoarthritis (OA), and explore whether this association, if causal, is mediated by systemic inflammatory biomarkers. Methods: In 281 Nor‐Hand study participants, we estimated associations between BMI and hand pain, as measured by the Australian/Canadian Osteoarthritis Hand Index (AUSCAN; range 0–20) and Numerical Rating Scale (NRS; range 0–10); foot pain, as measured by NRS (range 0–10); knee/hip pain, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; range 0–20); painful total body joint count; and pain sensitization. We fit natural‐effects models to estimate natural direct and natural indirect effects of BMI on pain through inflammatory biomarkers. Results: Each 5‐unit increase in BMI was associated with more severe hand pain (on average increased AUSCAN by 0.64 [95% confidence interval (95% CI) 0.23, 1.08]), foot pain (on average increased NRS by 0.65 [95% CI 0.36, 0.92]), knee/hip pain (on average increased WOMAC by 1.31 [95% CI 0.87, 1.73]), generalized pain, and pain sensitization. Mediation analyses suggested that the effects of BMI on hand pain and painful total body joint count were partially mediated by leptin and high‐sensitivity C‐reactive protein (hsCRP), respectively. Effect sizes for mediation by leptin were larger for the hands than for the lower extremities, and were statistically significant for the hands only. Conclusion: In people with hand OA, higher BMI is associated with greater pain severity in the hands, feet, and knees/hips. Systemic effects of obesity, measured by leptin, may play a larger mediating role for pain in the hands than in the lower extremities. Low‐grade inflammation, measured by hsCRP, may contribute to generalized pain in overweight/obese individuals. [ABSTRACT FROM AUTHOR]

Objective To investigate whether an ultrasound-guided treat-to-target strategy for early RA would lead to reduced MRI inflammation or less structural damage progression compared with a conventional treat-to-target strategy. Methods A total of 230 DMARD-naïve early RA patients were randomized to an ultrasound tight control strategy targeting DAS <1.6, no swollen joints and no power Doppler signal in any joint or a conventional strategy targeting DAS <1.6 and no swollen joints. Patients in both arms were treated according to the same DMARD escalation strategy. MRI of the dominant hand was performed at six time points over 2 years and scored according to the OMERACT RA MRI scoring system. A total of 218 patients had baseline and one or more follow-up MRIs and were included in the analysis. The mean MRI score change from baseline to each follow-up and the 2 year risk for erosive progression were compared between arms. Results MRI bone marrow oedema, synovitis and tenosynovitis improved over the first year and was sustained during the second year of follow-up, with no statistically significant differences between the ultrasound and the conventional arms at any time point. The 2 year risk for progression of MRI erosions was similar in both treatment arms: ultrasound arm 39%, conventional arm 33% [relative risk 1.16 (95% CI 0.81, 1.66), P  = 0.40]. Conclusion Incorporating ultrasound information in treatment decisions did not lead to reduced MRI inflammation or less structural damage compared with a conventional treatment strategy. The findings support that systematic use of ultrasound does not provide a benefit in the follow-up of patients with early RA. Trial registration number Clinicaltrials.gov, http://clinicaltrials.gov , NCT01205854. [ABSTRACT FROM AUTHOR]

Objectives To develop and test the reliability of a new semiquantitative scoring system for the assessment of cartilage changes by ultrasound in a web-based exercise as well as a patient exercise of patients with RA. Methods A taskforce of the Outcome Measures in Rheumatology Ultrasound Working Group performed a systematic literature review on the US assessment of cartilage in RA, followed by a Delphi survey on cartilage changes and a new semiquantitative US scoring system, and finally a web-based exercise as well as a patient exercise. For the web-based exercise, taskforce members scored a dataset of anonymized static images of MCP joints in RA patients and healthy controls, which also contained duplicate images. Subsequently, 12 taskforce members used the same US to score cartilage in MCP and proximal interphalangeal joints of six patients with RA in in a patient reliability exercise. Percentage agreement and prevalence of lesions were calculated, as intrareader reliability was assessed by weighted kappa and interreader reliability by Light's kappa. Results The three-grade semiquantitative scoring system demonstrated excellent intrareader reliability (kappa: 0.87 and 0.83) in the web-based exercise and the patient exercise, respectively. Interreader reliability was good in the web-based exercise (kappa: 0.64) and moderate (kappa: 0.48) in the patient exercise. Conclusion Our study demonstrates that ultrasound is a reliable tool for evaluating cartilage changes in the MCP joints of patients with RA and supports further development of a new reliable semiquantitative ultrasound scoring system for evaluating cartilage involvement in RA. [ABSTRACT FROM AUTHOR]

Background: A frequent observation in inflammatory conditions, including rheumatoid arthritis (RA), is low circulating amounts of pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B-6. Recently, a functional marker of vitamin B-6 status, the ratio of 3-hydroxykynurenine (HK): xanthurenic acid (XA) in plasma (HK: XA), was proposed.Objective: We investigated vitamin B-6 status in patients with RA before and after established treatment with TNFα inhibitors.Methods: We performed a longitudinal study of RA patients (n = 106, 36% men, median age 54 y) starting first treatment with a TNFα inhibitor (infliximab, etanercept, adalimumab, golimumab, or certolizumab). Clinical assessment (Disease Activity Score for 28 standard joints, DAS28), joint ultrasonography, and blood draw were performed at baseline and after 3 mo treatment. Plasma concentrations of PLP, HK, and XA were measured by liquid chromatography-tandem mass spectrometry. Associations of changes in vitamin B-6 markers with change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression.Results: At baseline PLP was inversely correlated with CRP (ρ = -0.27, P = 0.007), whereas HK: XA correlated with DAS28 (ρ = 0.46, P < 0.001), CRP (ρ = 0.36, P < 0.001), and ultrasonography scores (ρ = 0.29-0.35, P ≤ 0.003). After 3 mo treatment, the change (a 33% overall reduction) in DAS28 was related to changes in both PLP (ß = -0.28, P = 0.01) and HK: XA (ß = 0.33, P < 0.001). Good responders (45%) according to EULAR criteria experienced a 31% increase in PLP (P = 0.003) and an 11% decrease in HK: XA (P = 0.1), whereas nonresponders (24%) experienced a 25% increase in HK: XA (P = 0.02).Conclusion: Two independent measures of vitamin B-6 status confirm an association with disease activity in RA patients. The association of HK: XA with disease activity may also imply perturbations in kynurenine metabolism in RA. This trial was registered at helseforskning.etikkom.no as 2011/490. [ABSTRACT FROM AUTHOR]

Objectives To study prognostic factors for achievement of sustained remission in early RA patients receiving semi-personalized tight controlled treatment, and to assess the consistency of potential predictors across definitions of sustained remission. Methods DMARD-naïve early RA patients with symptom duration <2 years were treated according to a pre-defined algorithm within the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen trial. The algorithm allowed treatment adjustments based on established risk factors for a worse outcome. Multivariate logistic regression was used to examine baseline predictors of achieving sustained DAS remission at 16–24 months, and to assess predictors of secondary remission outcomes (all sustained 16–24 months): ACR/EULAR Boolean, Simplified Disease Activity Index (SDAI), no swollen joints and a composite outcome of DAS remission, no swollen joints and no radiographic progression. Results Of 222 patients, 118 (53%) reached sustained DAS remission, while 53 (24%) reached sustained ACR/EULAR Boolean and 73 (33%) sustained SDAI remission. More joint tenderness, assessed by Ritchie Articular Index, was a negative predictor of reaching sustained DAS remission (odds ratio (OR) = 0.90/U, 95% CI: 0.86, 0.94), sustained ACR/EULAR Boolean remission (OR = 0.92, 95% CI: 0.86, 0.98), sustained SDAI remission (OR = 0.94, 95% CI: 0.90, 1.00) as well as the two alternative definitions of sustained remission. Short symptom duration at baseline predicted sustained Boolean and SDAI remission. Other identified predictors were inconsistent across outcomes. Conclusion A higher tender joint score at baseline consistently reduced the chance of reaching sustained remission across all definitions. Our results support sustained remission as an achievable goal in early RA, especially when initiating DMARDs within 3 months symptom duration. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01205854 [ABSTRACT FROM AUTHOR]

Objective: Intraarticular glucocorticoid injections are common in rheumatoid arthritis (RA) treatment. This study was undertaken to investigate whether ultrasound in combination with clinical examination is better than clinical examination alone at identifying joints that will benefit from intraarticular injections, and to compare the efficacy of ultrasound‐guided versus palpation‐guided procedures. Methods: In the treat‐to‐target Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasonography in a Clinical Tight Control Regimen (ARCTIC), patients with early RA were randomized 1:1 to follow‐up with or without ultrasound. In addition to disease‐modifying antirheumatic drugs, intraarticular glucocorticoids were used to treat inflamed joints. The distribution of injections was assessed in both study groups. The relationship of clinical and ultrasound findings at the time of injection with treatment efficacy was examined, with non‐swollen joint at the next visit as the outcome measure. Treatment success was compared across study groups to evaluate ultrasound‐guided versus palpation‐guided procedures. Results: More injections were administered in the ultrasound group than in the conventional strategy group (n = 770 versus 548), especially in intercarpal joints (n = 58 versus 5) and metatarsophalangeal joints (n = 200 versus 104). Injecting clinically swollen joints without power Doppler (PD) activity on ultrasound was not efficacious compared to not injecting (odds ratio [OR] 1.3; P = 0.59). Efficacy was best in swollen joints (OR 9.0; P = 0.001) and non‐swollen joints (OR 8.4; P = 0.016) with moderate PD activity. Treatment success was similar for the ultrasound‐guided and palpation‐guided procedures. Conclusion: Our findings indicate that the efficacy of intraarticular glucocorticoid injections varies according to ultrasound findings at the time of injection, supporting the use of ultrasound as a tool to select joints that will benefit from intraarticular injections. However, ultrasound needle guidance was not superior to palpation guidance. [ABSTRACT FROM AUTHOR]

Objective: To perform external validation of a provisional definition of disease flare in patients with gout. Methods: Five hundred nine patients with gout were enrolled in a cross‐sectional study during a routine clinical care visit at 17 international sites. Data were collected to classify patients as experiencing or not experiencing a gout flare, according to a provisional definition. A local expert rheumatologist performed the final independent adjudication of gout flare status. Sensitivity, specificity, predictive values, and receiver operating characteristic (ROC) curves were used to determine the diagnostic performance of gout flare definitions. Results: The mean ± SD age of the patients was 57.5 ± 13.9 years, and 89% were male. The definition requiring fulfillment of at least 3 of 4 criteria (patient‐defined gout flare, pain at rest score of >3 on a 0–10‐point numerical rating scale, presence of at least 1 swollen joint, and presence of at least 1 warm joint) was 85% sensitive and 95% specific in confirming the presence of a gout flare, with an accuracy of 92%. The ROC area under the curve was 0.97. The definition based on a classification and regression tree algorithm (entry point, pain at rest score >3, followed by patient‐defined flare “yes”) was 73% sensitive and 96% specific. Conclusion: The definition of gout flare that requires fulfillment of at least 3 of 4 patient‐reported criteria is now validated to be sensitive, specific, and accurate for gout flares, as demonstrated using an independent large international patient sample. The availability of a validated gout flare definition will improve the ascertainment of an important clinical outcome in studies of gout. [ABSTRACT FROM AUTHOR]

The pro-inflammatory, leukocyte-derived S100A12 protein occurs as calcium-dependent oligomers in serum, while EDTA plasma from the majority of healthy individuals contains only monomers. Addition of 5 mM EDTA to serum leads to a rapid dissociation of the oligomers in most samples. However, using gel permeation chromatography, we have found that sera from some patients and seemingly healthy individuals contain molecular complexes in the 400-1000 kDa range reacting with anti-S100A12 even in the presence of EDTA; for these we introduce the name ERAC ( EDTA Resistant S100 A12 Complexes). Based upon monoclonal antibodies and the lateral flow principle, we have developed a quantitative rapid ERAC test giving results within 10 minutes. The highest prevalence of ERAC positivity was found in sera from patients with concomitant rheumatoid arthritis and coronary heart disease. The structure of ERAC is not yet known. Further studies are needed to analyse the mechanism behind the appearance of ERAC and the possible association with inflammatory-related diseases. [ABSTRACT FROM AUTHOR]

Objectives. To document the practice and training opportunities of US-guided arthrocentesis and joint injection (UGAJ) among rheumatologists in the member countries of the European League Against Rheumatism (EULAR).Methods. An English-language questionnaire, containing questions on demographics, clinical and practical aspects of UGAJ, training options in UGAJ for rheumatologists, UGAJ education in the rheumatology training curriculum and other structured education programmes in UGAJ was sent to three different groups: (i) all national rheumatology societies of EULAR; (ii) all national societies of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB); and (iii) 22 senior rheumatologists involved in EULAR musculoskeletal US training from 14 European countries, who were also asked to circulate the questionnaire among relevant colleagues.Results. Thirty-three (75%) of 44 countries responded to the questionnaire (61.3% of national rheumatology societies, 25% of the national US societies and 100% of expert ultrasonographers). In the majority of countries (85%) <10% of rheumatologists routinely perform UGAJ in clinical practice, while the remaining countries (15%) reported a rate of 10–50%. The percentage of rheumatologists receiving training in UGAJ was <10% in the majority (72.7%) of countries.Conclusion. The study highlights the relatively low prevalence of UGAJ as compared with the high (>80%) rate of rheumatologists performing conventional joint injection in most of the surveyed countries. The reported variations in practice and the lack of available structured training programmes for trainees in most countries indicates the need for standardization in areas including training guidelines. [ABSTRACT FROM PUBLISHER]

Objective. To document the current state of musculoskeletal US (MSUS) training and extent of implementation among rheumatologists in the member countries of EULAR.Methods. An English-language questionnaire, divided into five sections (demographics, clinical use of MSUS, overall MSUS training for rheumatologists, MSUS education in the rheumatology training curriculum and education in MSUS offered by the national rheumatology society) was sent by e-mail to three different groups: (i) all national rheumatology societies of EULAR; (ii) all national societies of the European Federation of Societies for Ultrasound in Medicine and Biology; and (iii) 19 senior rheumatologists involved in MSUS training from 14 European countries.Results. Thirty-one (70.5%) out of 44 countries responded to the questionnaire (59.1% of national rheumatology societies, 34.5% of the national US societies and 100% of expert ultrasonographers). Rheumatology was listed among medical specialities that mainly perform MSUS in 20 (64.5%) countries; however, in most [19 (63.3%)] countries <10% of rheumatologists routinely perform MSUS in clinical practice. Training varies widely from country to country, with low rates of competency assessment. MSUS education is part of the rheumatology training curriculum in over half the surveyed countries, being compulsory in 7 (22.6%) countries and optional in 11 (35.5%).Conclusions. This study confirms the high uptake of MSUS across Europe. The reported variation in training and practice between countries suggests a need for standardization in areas including training guidelines. [ABSTRACT FROM PUBLISHER]