Hand osteoarthritis phenotypes based on a biopsychosocial approach, and their associations with cross-sectional and longitudinal pain.

OBJECTIVE: Hand osteoarthritis (OA) pain is characterized as heterogeneous and multifactorial. Differences in pain may be explained by underlying phenotypes, which have not been previously explored DESIGN: Latent class analysis determined classes of participants with hand OA from the Nor-Hand study baseline examination (2016-17) based on a biopsychosocial framework. Outcomes were hand and overall bodily pain intensity (Numeric Rating Scale, 0-10) at baseline and follow-up (2019-21), The relations of the classes to pain outcomes at baseline, follow-up, and change over time were analysed in separate models by linear regression, using the overall healthiest class as reference. RESULTS: Five classes differing in radiographic hand OA burden and OA burden in the lower extremities by ultrasound, demographic factors, psychosocial burden and pain sensitization was identified. Persons with the least severe OA but higher burden of biopsychosocial factors reported the most hand pain (beta 3.65, 95% CI 2.53, 4.75). Pain was less pronounced in persons with the most severe hand OA but low burden of biopsychosocial factors (beta 1.03, 95% CI 0.41, 1.65). Results were similar for overall bodily pain and at follow-up. Changes in pain were small, but the association between a separate class defined by higher levels of biopsychosocial burden and pain changes was significant. CONCLUSION: The five hand OA phenotypes were associated with pain at baseline and 3.5 years later. The phenotype with the least OA severity, but higher burden of biopsychosocial factors reported more pain than the phenotype with the most severe OA, reflecting the symptom-structure discordance of the hand OA pain experience.

Adding ultrasound to treat-to-target shows no benefit in achieving clinical remission nor in slowing radiographic progression in rheumatoid arthritis: results from a multicenter prospective cohort.

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 [ß(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.

Stricter treat-to-target in RA does not result in less radiographic progression: a longitudinal analysis in RA BIODAM.

OBJECTIVES: To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. METHODS: Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. RESULTS: In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: -0.04, 0.33) for 2 vs 0 visits; and +0.08 units (-0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. CONCLUSIONS: In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.

Associations of Body Mass Index With Pain and the Mediating Role of Inflammatory Biomarkers in People With Hand Osteoarthritis.

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.

Ultrasonography of Inflammatory and Structural Lesions in Hand Osteoarthritis: An Outcome Measures in Rheumatology Agreement and Reliability Study.

OBJECTIVE: To standardize and assess the reliability of ultrasonographic assessment of inflammatory and structural lesions in patients with hand osteoarthritis (OA). METHODS: The Outcome Measures in Rheumatology Ultrasound Working Group selected synovial hypertrophy (SH), joint effusion (JE), and power Doppler (PD) signals as the main inflammatory lesions in hand OA, and suggested osteophytes in the scapho-trapezio-trapezoid (STT) and cartilage defects in the proximal interphalangeal (PIP) joints as novel additions to previous structural scoring systems. A complementary imaging atlas provided detailed examples of the scores. A reliability exercise of static images was performed for the inflammatory features, followed by a patient-based exercise with 6 sonographers testing inflammatory and structural features in 12 hand OA patients. We used Cohen's kappa for intrareader and Light's kappa for interreader reliability for all features except PD, in which prevalence-adjusted bias-adjusted kappa (PABAK) was applied. Percentage agreement was also assessed. RESULTS: The web-based reliability exercise demonstrated substantial intra- and interreader reliability for all inflammatory features (κ > 0.64). In the patient-based exercise, intra- and interreader reliability, respectively, varied: SH κ = 0.73 and 0.45; JE κ = 0.70 and 0.55; PD PABAK = 0.90 and 0.88; PIP joint cartilage κ = 0.56 and 0.45; and STT osteophytes κ = 0.62 and 0.36. Percentage close agreement was high for all features (>85%). CONCLUSION: With ultrasound, substantial to excellent intrareader reliability was found for inflammatory features of hand OA. Interreader reliability was moderate, but overall high close agreement between readers suggests that better reliability is achievable after further training. Assessment of osteophytes in the STT joint and cartilage in the PIP joints achieved less reliability and the latter is not endorsed.

The EFSUMB Guidelines and Recommendations for Musculoskeletal Ultrasound - Part II: Joint Pathologies, Pediatric Applications, and Guided Procedures.

The second part of the Guidelines and Recommendations for Musculoskeletal Ultrasound (MSUS), produced under the auspices of EFSUMB, following the same methodology as for Part 1, provides information and recommendations on the use of this imaging modality for joint pathology, pediatric applications, and musculoskeletal ultrasound-guided procedures. Clinical application, practical points, limitations, and artifacts are described and discussed for every joint or procedure. The document is intended to guide clinical users in their daily practice.

The EFSUMB Guidelines and Recommendations for Musculoskeletal Ultrasound - Part I: Extraarticular Pathologies.

The first part of the guidelines and recommendations for musculoskeletal ultrasound, produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), provides information about the use of musculoskeletal ultrasound for assessing extraarticular structures (muscles, tendons, entheses, ligaments, bones, bursae, fasciae, nerves, skin, subcutaneous tissues, and nails) and their pathologies. Clinical applications, practical points, limitations, and artifacts are described and discussed for every structure. After an extensive literature review, the recommendations have been developed according to the Oxford Centre for Evidence-based Medicine and GRADE criteria and the consensus level was established through a Delphi process. The document is intended to guide clinical users in their daily practice.

Bone Erosions Detected by Ultrasound Are Prognostic for Clinical Arthritis Development in Patients With ACPA and Musculoskeletal Pain.

Anti-citrullinated protein antibodies (ACPA) often precede onset of rheumatoid arthritis (RA) by years, and there is an urgent clinical need for predictors of arthritis development among such at-risk patients. This study assesses the prognostic value of ultrasound for arthritis development among ACPA-positive patients with musculoskeletal pain. We prospectively followed 82 ACPA-positive patients without clinical signs of arthritis at baseline. Ultrasound at baseline assessed synovial hypertrophy, inflammatory activity by power Doppler, and erosions in small joints of hands and feet. We applied Cox regression analyses to examine associations with clinical arthritis development during follow-up (median, 69 months; range, 24-90 months). We also compared the ultrasound findings among the patients to a control group of 100 blood donors without musculoskeletal pain. Clinical arthritis developed in 39/82 patients (48%) after a median of 6 months (range, 1-71 months). One or more ultrasound erosions occurred in 13/82 patients (16%), with none in control subjects (p < 0.001). Clinical arthritis development was more common among patients with baseline ultrasound erosions than those without (77 vs. 42%, p = 0.032), and remained significant in a multivariable Cox regression analysis that included previously described prognostic factors (HR 3.9, 95% CI 1.6-9.4, p = 0.003). Ultrasound-detected tenosynovitis was more frequent among the patients and associated with clinical arthritis development in a univariable analysis (HR 2.5, 95% CI 1.1-5.7, p = 0.031), but did not remain statistically significant in multivariable analysis. Thus, bone erosions detected by ultrasound are independent predictors of clinical arthritis development in an ACPA-positive at-risk population. Trial Registration: Regional Ethics Committee in Linköping, Sweden, Dnr M220-09. Registered 16 December 2009, https://etikprovningsmyndigheten.se/.

Consensus-based semi-quantitative ultrasound scoring system for gout lesions: Results of an OMERACT Delphi process and web-reliability exercise.

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.

Flare Rate Thresholds for Patient Assessment of Disease Activity States in Gout.

OBJECTIVE: To determine the relationship between gout flare rate and self-categorization into remission, low disease activity (LDA), and patient acceptable symptom state (PASS). METHODS: Patients with gout self-categorized as remission, LDA, and PASS, and reported number of flares over the preceding 6 and 12 months. Multinomial logistic regression was used to determine the association between being in each disease state (LDA and PASS were combined) and flare count, and self-reported current flare. A distribution-based approach and extended Youden index identified possible flare count thresholds for each state. RESULTS: Investigators from 17 countries recruited 512 participants. Remission was associated with a median recalled flare count of zero over both 6 and 12 months. Each recalled flare reduced the likelihood of self-perceived remission compared with being in higher disease activity than LDA/PASS, by 52% for 6 months and 23% for 12 months, and the likelihood of self-perceived LDA/PASS by 15% and 5% for 6 and 12 months, respectively. A threshold of 0 flares in preceding 6 and 12 months was associated with correct classification of self-perceived remission in 58% and 56% of cases, respectively. CONCLUSION: Flares are significantly associated with perceptions of disease activity in gout, and no flares over the prior 6 or 12 months is necessary for most people to self-categorize as being in remission. However, recalled flare counts alone do not correctly classify all patients into self-categorized disease activity states, suggesting that other factors may also contribute to self-perceived gout disease activity.

Contemporary imaging of rheumatoid arthritis: Clinical role of ultrasound and MRI.

Magnetic resonance imaging (MRI) and musculoskeletal ultrasound (MSUS) are sensitive imaging modalities used by clinicians to assist in decision-making in the management of rheumatoid arthritis (RA). This review will examine the utility of MRI and MSUS in diagnosing RA, predicting RA flares, tapering therapy, assessing remission, and examining difficult periarticular features. We will also outline the strengths and weaknesses of utilizing MRI and MSUS as outcome measures in the management of RA.

Conventional versus ultrasound treat to target: no difference in magnetic resonance imaging inflammation or joint damage over 2 years in early rheumatoid arthritis.

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.

Associations Between Ultrasound-Detected Synovitis, Pain, and Function in Interphalangeal and Thumb Base Osteoarthritis: Data From the Nor-Hand Cohort.

OBJECTIVE: To explore whether ultrasound-detected gray-scale synovitis and power Doppler activity in the interphalangeal and first carpometacarpal (CMC1) joints are associated with pain and physical function in patients with hand osteoarthritis (OA). METHODS: A total of 290 patients with hand OA underwent an ultrasound examination of the bilateral interphalangeal and CMC1 joints. Using logistic regression analyses with generalized estimating equations, we examined whether grade 0-3 gray-scale synovitis and power Doppler activity were associated with pain in the same joint. Using linear regression analyses, we examined whether the degree of inflammation was associated with numeric rating scale and Australian/Canadian (AUSCAN) Osteoarthritis Hand Index hand pain, AUSCAN physical function, and grip strength scores. Analyses were made separately for interphalangeal and CMC1 joints, and adjusted for age, sex, body mass index, psychosocial factors, use of analgesics, and presence of osteophytes. RESULTS: At joint level, increasing gray-scale synovitis severity was associated with higher odds of pain upon palpation in both the interphalangeal (grade 2-3; odds ratio [OR] 3.17 [95% confidence interval (95% CI) 2.35, 4.28]) and CMC1 joints (grade 2-3; OR 4.40 [95% CI 2.10, 9.24]). Similar associations were found for power Doppler activity and joint pain in the previous 24 hours and 6 weeks. Power Doppler activity in CMC1 was also related to overall hand pain/physical function and lower grip strength. CONCLUSION: Inflammation in both the interphalangeal and CMC1 joints was associated with pain in the same joint. However, associations with hand pain, reduced physical function, and lower grip strength were only present for inflammation in the CMC1 joints, suggesting that lowering CMC1 inflammation is an important treatment target.

Tender Joint Count and Inflammatory Activity in Patients With Established Rheumatoid Arthritis: Results From a Longitudinal Study.

OBJECTIVE: The tender joint count (TJC) is included in composite disease activity scores (CDAS) (the Disease Activity Score in 28 joints, the Clinical Disease Activity Index, and the Simplified Disease Activity Index). The impact of having predominantly tender joints was explored by use of the Tender-Swollen Joint Count Difference (TSJD), and ultrasound (US) provided a measure of joint inflammation. The current study aimed to explore the cross-sectional and longitudinal associations between the TSJD and a spectrum of outcome measures, including US scores in patients with established rheumatoid arthritis (RA) during follow-up and while receiving treatment with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: This was an observational study of 209 patients with established RA consecutively included upon initiation of bDMARD treatment and followed-up with clinical, laboratory, and comprehensive US examinations at 0, 1, 2, 3, 6, and 12 months. Patients were categorized into 2 groups: those with predominantly tender joints (TSJD >0) and those with predominantly swollen joints (TSJD ≤0). Statistical analyses included Pearson's correlation coefficient, an independent samples t-test, and regression analyses. RESULTS: The TJC had high correlations only with patient-reported outcomes (PROMs) (P < 0.001). Levels from CDAS and PROMs were significantly higher (P < 0.001) at all visits in patients with TSJD >0 compared to those with TSJD <0. Laboratory markers and assessor's global visual analog scale scores were similar, and US sum scores were significantly lower (P < 0.001-0.03). The baseline TSJD positively predicted levels of all CDAS at 6 months (P < 0.001-0.019) but was a negative predictor of US sum scores (gray-scale and power Doppler) at 6 and 12 months (P < 0.001). CONCLUSION: Patients with predominantly tender joints had higher CDAS but lower levels of inflammation as defined by US. These findings indicate that inclusion of the TJC in the CDAS may contribute to misleading information about inflammatory activity.

Assessing synovitis in the hands in patients with rheumatoid arthritis by ultrasound: an agreement study exploring the most inflammatory active side from two Norwegian trials.

OBJECTIVE: To assess if the right hand, the dominant hand, or the hand with more clinically swollen joints (SwJ) is per se the most inflamed and exhibits the greatest change during treatment and hence preferred for unilateral scoring of synovitis by ultrasound in rheumatoid arthritis (RA) patients. METHODS: Using data from two previously published Norwegian RA patient cohorts initiating treatment, bilateral metacarpophalangeal joint 1-5, proximal phalangeal joint 2+3, and wrists were evaluated by ultrasound. Using a 0-3 scoring system a grey-scale (GS), power Doppler (PD) and global synovitis score (GLOESS) was calculated for each hand (0-30). For precision, a difference of < ± 3 in sum score was pre-specified as indicating clinically insignificant difference in inflammatory activity for all three scores. RESULTS: Four hundred thirty-seven RA patients were included. Baseline ultrasound inflammation was statistically significantly higher in hands with more vs fewer SwJ ([mean difference, 95%CI] GS sum score 2.21[1.30 to 3.12], PD sum score 1.70 [0.94 to 2.47] and GLOESS 2.31[1.36 to 3.26]) and also exhibited significantly more change for all sum scores at 3 months follow-up (GS sum score 1.34 [0.60 to 2.08], PD sum score 1.17 [0.44 to 1.91], and GLOESS 1.43 [0.63 to 2.22]). No such differences were found between the dominant and the non-dominant or the right and the left hands at any time points. CONCLUSION: The hand with clinically more SwJ is statistically more inflammatory active according to GS, Doppler, and GLOESS sum scores, exhibits a change during treatment, and is potentially the best choice for unilateral scoring systems.

Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors.

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.

Development of semiquantitative ultrasound scoring system to assess cartilage in rheumatoid arthritis.

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.

OMERACT Definitions for Ultrasonographic Pathologies and Elementary Lesions of Rheumatic Disorders 15 Years On.

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Working Group (WG) operates research activities for the validation of US as an outcome measurement instrument according to the Filter 2.0 framework. METHODS: Original publications on definitions and scoring systems for pathophysiological manifestations and elementary lesions of various rheumatic disorders were reviewed from the onset of the WG research in 2005. RESULTS: Definitions and scoring systems according to new terminology are provided. CONCLUSION: We have redefined OMERACT US pathology and elementary lesions as well as scoring systems, which are now proposed for OMERACT approval for application in clinical trials.

Ultrasound of Subtalar Joint Synovitis in Patients with Rheumatoid Arthritis: Results of an OMERACT Reliability Exercise Using Consensual Definitions.

OBJECTIVE: To evaluate the intraobserver and interobserver reliability of the ultrasonographic (US) assessment of subtalar joint (STJ) synovitis in patients with rheumatoid arthritis (RA). METHODS: Following a Delphi process, 12 sonographers conducted an US reliability exercise on 10 RA patients with hindfoot pain. The anteromedial, posteromedial, and posterolateral STJ was assessed using B-mode and power Doppler (PD) techniques according to an agreed US protocol and using a 4-grade semiquantitative grading score for synovitis [synovial hypertrophy (SH) and signal] and a dichotomous score for the presence of joint effusion (JE). Intraobserver and interobserver reliability were computed by Cohen's and Light's κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. RESULTS: Mean weighted Cohen's κ for SH, PD, and JE were 0.80 (95% CI 0.62-0.98), 0.61 (95% CI 0.48-0.73), and 0.52 (95% CI 0.36-0.67), respectively. Weighted Cohen's κ for SH, PD, and JE in the anteromedial, posteromedial, and posterolateral STJ were -0.04 to 0.79, 0.42-0.95, and 0.28-0.77; 0.31-1, -0.05 to 0.65, and -0.2 to 0.69; 0.66-1, 0.52-1, and 0.42-0.88, respectively. Weighted Light's κ for SH was 0.67 (95% CI 0.58-0.74), 0.46 (95% CI 0.35-0.59) for PD, and 0.16 (95% CI 0.08-0.27) for JE. Weighted Light's κ for SH, PD, and JE were 0.63 (95% CI 0.45-0.82), 0.33 (95% CI 0.19-0.42), and 0.09 (95% CI -0.01 to 0.19), for the anteromedial; 0.49 (95% CI 0.27-0.64), 0.35 (95% CI 0.27-0.4), and 0.04 (95% CI -0.06 to 0.1) for posteromedial; and 0.82 (95% CI 0.75-0.89), 0.66 (95% CI 0.56-0.8), and 0.18 (95% CI 0.04-0.34) for posterolateral STJ, respectively. CONCLUSION: Using a multisite assessment, US appears to be a reliable tool for assessing synovitis of STJ in RA.