2023 EULAR classification criteria for hand osteoarthritis.

OBJECTIVES: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features. METHODS: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. RESULTS: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. CONCLUSIONS: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology.

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

MRI-based Synthetic CT in the Detection of Structural Lesions in Patients with Suspected Sacroiliitis: Comparison with MRI.

Background Evaluation of structural lesions in the sacroiliac (SI) joints can improve the accuracy for diagnosis of spondyloarthritis. However, structural lesions, such as erosions, are difficult to assess on routine T1-weighted MRI scans. Purpose To determine the diagnostic performance of MRI-based synthetic CT (sCT) in the depiction of erosions, sclerosis, and ankylosis of the SI joints compared with T1-weighted MRI, with CT as the reference standard. Materials and Methods A prospective study (clinical trial registration no. B670201837885) was performed from February 2019 to November 2019. Adults were referred from a tertiary hospital rheumatology outpatient clinic with clinical suspicion of inflammatory sacroiliitis. MRI and CT of the SI joints were performed on the same day. SCT images were generated from MRI scans using a commercially available deep learning-based image synthesis method. Two readers independently recorded if structural lesions (erosions, sclerosis, and ankylosis) were present on T1-weighted MRI, sCT, and CT scans in different reading sessions, with readers blinded to clinical information and other images. Diagnostic performance of sCT and T1-weighted MRI scans were analyzed using generalized estimating equation models, with consensus results of CT as the reference standard. Results Thirty participants were included (16 men, 14 women; mean age, 40 years ± 10 [standard deviation]). Diagnostic accuracy of sCT was higher than that of T1-weighted MRI for erosion (94% vs 86%, P = .003), sclerosis (97% vs 81%, P < .001), and ankylosis (92% vs 84%, P = .04). With sCT, specificity for erosion detection (96% [95% CI: 90, 98] vs 89% [95% CI: 81, 94], P = .01] and sensitivity for detection of sclerosis [94% [95% CI: 87, 97] vs 20% [95% CI: 10, 35], P < .001] and ankylosis (93% [95% CI: 78, 98] vs 70% [95% CI: 47, 87], P = .001) were improved. Conclusion With CT as the reference standard, synthetic CT of the sacroiliac joints has better diagnostic performance in the detection of structural lesions in individuals suspected of having sacroiliitis compared with routine T1-weighted MRI. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Fritz in this issue.

Topographical analysis of structural lesions between dominant and non-dominant hands in erosive osteoarthritis.

KEY MESSAGES: No difference between both hands was observed for clinical and radiographical presentations in EHOA patients. A bilateral and symmetrical relationship was found between hand joints. HIGHLIGHTS: EHOA have symmetrical distribution and specific association in structural lesions. This study aims to analyse the preferential topographical distribution of clinical and structural lesions between the dominant and non-dominant hands in erosive hand osteoarthritis (EHOA) patients. Both hands were assessed via radiography in EHOA patients. A comparative analysis of the clinical features and structural lesions between the dominant and non-dominant hands was performed. The structural lesions were assessed according to the anatomical radiographic score of Verbruggen-Veys (VV). Next, a principal component analysis was performed to describe and highlight the relationships observed between the joints. Sixty patients were included in this study: there were 57 women, and the mean age was 66.1 (± 7.6) years. For the distal interphalangeal (DIP) joints, nodes were observed more frequently on the dominant hand (4 vs 3; p = 0.005). No difference in structural lesions was observed between the two hands except for the 2nd proximal interphalangeal (PIP) (p = 0.045). A principal component analysis with varimax rotation described relationships between the 2nd PIP, 3rd PIP, 4th PIP, 4th DIP and 5th DIP joints in both hands. No significant differences between dominant and non-dominant hands were observed for clinical and structural lesions in our sample of EHOA patients. A bilateral and symmetrical injury was observed in most EHOA joints. Trial registration Clinical trial registration number: NCT01068405.

2018 update of the EULAR recommendations for the management of hand osteoarthritis.

Since publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these recommendations. EULAR standardised operating procedures were followed. A systematic literature review was performed, collecting the evidence regarding all non-pharmacological, pharmacological and surgical treatment options for hand OA published to date. Based on the evidence and expert opinion from an international task force of 19 physicians, healthcare professionals and patients from 10 European countries formulated overarching principles and recommendations. Level of evidence, grade of recommendation and level of agreement were allocated to each statement. Five overarching principles and 10 recommendations were agreed on. The overarching principles cover treatment goals, information provision, individualisation of treatment, shared decision-making and the need to consider multidisciplinary and multimodal (non-pharmacological, pharmacological, surgical) treatment approaches. Recommendations 1-3 cover different non-pharmacological treatment options (education, assistive devices, exercises and orthoses). Recommendations 4-8 describe the role of different pharmacological treatments, including topical treatments (preferred over systemic treatments, topical non-steroidal anti-inflammatory drugs (NSAIDs) being first-line choice), oral analgesics (particularly NSAIDs to be considered for symptom relief for a limited duration), chondroitin sulfate (for symptom relief), intra-articular glucocorticoids (generally not recommended, consider for painful interphalangeal OA) and conventional/biological disease-modifying antirheumatic drugs (discouraged). Considerations for surgery are described in recommendation 9. The last recommendation relates to follow-up. The presented EULAR recommendations provide up-to-date guidance on the management of hand OA, based on expert opinion and research evidence.

Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1ß dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis.

OBJECTIVE: To assess the efficacy, safety, pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1α/ß dual variable domain immunoglobulin lutikizumab (ABT-981) in erosive hand osteoarthritis (HOA). METHODS: Patients with ≥1 erosive and ≥3 tender and/or swollen hand joints were randomised to placebo or lutikizumab 200 mg subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain score from baseline to 16 weeks. At baseline and week 26, subjects had bilateral hand radiographs and MRI of the hand with the greatest number of baseline tender and/or swollen joints. Continuous endpoints were assessed using analysis of covariance models, with treatment and country as main factors and baseline measurements as covariates. RESULTS: Of 132 randomised subjects, 1 received no study drug and 110 completed the study (placebo, 61/67 (91%); lutikizumab, 49/64 (77%)). AUSCAN pain was not different among subjects treated with lutikizumab versus placebo at week 16 (least squares mean difference, 1.5 (95% CI -1.9 to 5.0)). Other clinical and imaging endpoints were not different between lutikizumab and placebo. Lutikizumab significantly decreased serum high-sensitivity C reactive protein levels, IL-1α and IL-1ß levels, and blood neutrophils. Lutikizumab pharmacokinetics were consistent with phase I studies and not affected by antidrug antibodies. Injection site reactions and neutropaenia were more common in the lutikizumab group; discontinuations because of adverse events occurred more frequently with lutikizumab (4/64) versus placebo (1/67). CONCLUSION: Despite adequate blockade of IL-1, lutikizumab did not improve pain or imaging outcomes in erosive HOA compared with placebo.

Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial.

OBJECTIVE: Hand osteoarthritis is a prevalent disease with limited treatment options. Since joint inflammation is often present, we investigated tumour necrosis factor (TNF) as treatment target in patients with proven joint inflammation in a proof-of-concept study. METHODS: This 1-year, double-blind, randomised, multicentre trial (NTR1192) enrolled patients with symptomatic erosive inflammatory hand osteoarthritis. Patients flaring after non-steroidal anti-inflammatory drug washout were randomised to etanercept (24 weeks 50 mg/week, thereafter 25 mg/week) or placebo. The primary outcome was Visual Analogue Scale (VAS) pain at 24 weeks. Secondary outcomes included clinical and imaging outcomes (radiographs scored using Ghent University Scoring System (GUSS, n=54) and MRIs (n=20)). RESULTS: Of 90 patients randomised to etanercept (n=45) or placebo (n=45), respectively, 12 and 10 discontinued prematurely. More patients on placebo discontinued due to inefficacy (6 vs 3), but fewer due to adverse effects (1 vs 6). The mean between-group difference (MD) in VAS pain was not statistically significantly different (-5.7 (95% CI -15.9 to 4.5), p=0.27 at 24 weeks; - 8.5 (95% CI -18.6 to 1.6), p=0.10 at 1 year; favouring etanercept). In prespecified per-protocol analyses of completers with pain and inflammation at baseline (n=61), MD was -11.8 (95% CI -23.0 to -0.5) (p=0.04) at 1 year. Etanercept-treated joints showed more radiographic remodelling (delta GUSS: MD 2.9 (95% CI 0.5 to 5.4), p=0.02) and less MRI bone marrow lesions (MD -0.22 (95% CI -0.35 to -0.09), p = 0.001); this was more pronounced in joints with baseline inflammation. CONCLUSION: Anti-TNF did not relieve pain effectively after 24 weeks in erosive osteoarthritis. Small subgroup analyses showed a signal for effects on subchondral bone in actively inflamed joints, but future studies to confirm this are warranted.

RANKL blockade for erosive hand osteoarthritis: a randomized placebo-controlled phase 2a trial.

Erosive hand osteoarthritis (OA) is a prevalent and disabling disease with limited treatment options. Here we present the results of a monocentric, placebo-controlled, double-blind, randomized phase 2a clinical trial with denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, evaluating the effects on structure modification in erosive hand OA. Patients were randomized to 48 weeks treatment with denosumab 60 mg every 3 months (n = 51, 41 females) or placebo (n = 49, 37 females). The primary (radiographic) endpoint was the change in the total Ghent University Scoring System (GUSS) at week 24, where positive changes correspond to remodeling and negative changes to erosive progression. Secondary endpoints were the change in the GUSS at week 48 and the number of new erosive joints at week 48 by the anatomical phase scoring system. Baseline mean GUSS (standard deviation) of target joints was 155.9 (69.3) in the denosumab group and 158.7 (46.8) in the placebo group. The primary endpoint was met with an estimated difference between groups of 8.9 (95% confidence interval (CI) 1.0 to 16.9; P = 0.024) at week 24. This effect was confirmed at week 48 (baseline adjusted GUSS (standard error of the mean) denosumab and placebo were 163.5 (2.9) and 149.2 (3.9), respectively; with an estimated difference between groups of 14.3 (95% CI 4.6 to 24.0; P = 0.003)). At patient level, more new erosive joints were developed in the placebo group compared with denosumab at week 48 (odds ratio 0.24 (95% CI 0.08 to 0.72); P = 0.009). More adverse events occurred in the placebo group (125 events in 44 patients (90%)) compared with the denosumab group (97 events in 41 patients (80%)). These results demonstrate that denosumab has structure modifying effects in erosive hand OA by inducing remodeling and preventing new erosive joints. EU Clinical Trials Register identifier 2015-003223-53 .

Neuropathic-like pain in knee osteoarthritis: exploring differences in knee loading and inflammation. A cross-sectional study.

BACKGROUND: A subgroup of patients with knee osteoarthritis (OA) reports symptoms attributable to a neuropathic cause. Little to no attention has been invested on investigating differences in knee loading and inflammation in these patients. AIM: To explore differences in inflammation and knee loading in patients with knee OA categorized based on the presence of neuropathic-like pain. DESIGN: Cross-sectional study. SETTING: Ghent University Hospital, Ghent, Belgium. POPULATION: Knee OA patients. METHODS: cross-sectional analysis of data from 96 patients (mean age 64.18±7.11 years) with primary knee OA participating in a randomized controlled trial. Participants were divided into three groups (unlikely, possible and indication of neuropathic-like pain) according to the modified painDETECT questionnaire (mPDQ). Data on demographics, symptoms and physical function were obtained by questionnaires. Effusion/synovitis and bone marrow lesions (BMLs) were measured using magnetic resonance imaging. Knee loading variables (knee adduction moment [KAM], KAM impulse, and knee flexion moment [KFM]) were assessed by 3D-motion analysis. One-way analysis of covariance (ANCOVA), Chi-square test and curve analyses were used to analyze continuous, categorical and loading variables respectively. Multinomial logistic regression was used to identify predictors for neuropathic-like pain. RESULTS: Patients with indication of neuropathic-like pain exhibited higher KAM impulse compared to those with no indication of neuropathic-like pain (standard mean difference (SMD): -0.036 Nm normalized to body weight and height per second, 95% CI: -0.071, -0.001) along with greater pain intensity (SMD: 3.87 units, 95% CI: 1.90, 5.84), stiffness (SMD: 1.34 units, 95% CI: 0.19, 2.48) and worse physical function (SMD: 13.98 units 95% CI: 7.52, 20.44). Curve analysis showed no significant differences in KFM and KAM between groups. Effusion/synovitis and BMLs did not differ significantly between groups. The best predictors for indication of neuropathic-like pain were KAM impulse, Hoffa and sex. CONCLUSIONS: Knee OA patients with indication of neuropathic-like pain exhibited higher dynamic medial loading, greater pain severity and worse physical function, while inflammatory markers were not significantly different across mPDQ groups. Future longitudinal studies are warranted to strengthen the evidence and establish mechanisms to explain associations between neuropathic-like pain and knee loading. CLINICAL REHABILITATION IMPACT: Knee loading is a modifiable factor and patients with neuropathic-like pain may benefit from offloading interventions.

Predictors of functional impairment and pain in erosive osteoarthritis of the interphalangeal joints: comparison with controlled inflammatory arthritis.

OBJECTIVE: To compare levels of pain and functional limitation in patients with erosive osteoarthritis (OA) of the interphalangeal finger joints with those in patients with nonerosive OA and patients with controlled inflammatory arthritis affecting the hands, and to explore predictors of functional impairment in erosive OA. METHODS: A cross-sectional study including 270 patients with OA of the hands who were referred to rheumatology clinics was performed. A group of patients with inflammatory arthritis (rheumatoid arthritis or psoriatic arthritis) with a low Disease Activity Score in 28 joints (<3.2; n = 79) was examined. Levels of functional impairment (measured by the Functional Index for Hand OA [FIHOA] and Australian/Canadian OA Hand Index [AUSCAN]) and pain were compared between the groups. Predictors of functional impairment in erosive OA were evaluated by generalized linear models. RESULTS: Of 270 patients with hand OA, 167 (61.9%) were classified as having erosive OA. Despite a higher percentage of patients taking analgesics (almost 60%), patients with erosive OA had worse functional outcome and pain scores than patients with controlled inflammatory arthritis or nonerosive OA. Pain scores remained significantly higher in patients with erosive OA after correction for potential confounders. FIHOA and AUSCAN function scores showed a trend toward more disability in patients with erosive OA. Female sex and the number of radiographic affected joints (consisting of joints in the erosive and remodeled radiographic phases) were the strongest predictors of functional impairment in erosive OA. Whether the carpometacarpal joints were affected did not influence functional status in patients with erosive OA. CONCLUSION: Our findings indicate that patients with erosive OA have more functional impairment and significantly more pain compared to patients with controlled inflammatory arthritis affecting the hands. This highlights the significant clinical burden of erosive OA and warrants the search for new treatment strategies.

Associations between markers of inflammation and altered pain perception mechanisms in people with knee osteoarthritis: a systematic review.

To provide an extensive review on the associations between knee inflammation and altered pain perception mechanisms in people with knee osteoarthritis (OA). MEDLINE, Web of Science, EMBASE and Scopus were searched up to 13 December 2022. We included articles reporting associations between knee inflammation (measured by effusion, synovitis, bone marrow lesions (BMLs) and cytokines) and signs of altered pain processing (assessed by quantitative sensory testing and/or questionnaire for neuropathic-like pain) in people with knee OA. Methodological quality was evaluated using the National Heart, Lung and Blood Institute Study Quality Assessment Tool. Level of evidence and strength of conclusion were determined using the Evidence-Based Guideline Development method. Nine studies were included, comprising of 1889 people with knee OA. Signs of greater effusion/synovitis may be positively associated with lower knee pain pressure threshold (PPT) and neuropathic-like pain. Current evidence could not establish an association between BMLs and pain sensitivity. Evidence on associations between inflammatory cytokines and pain sensitivity or neuropathic-like pain was conflicting. There are indications of a positive association between higher serum C reactive protein (CRP) levels and lower PPT and presence of temporal summation. Methodological quality varied from level C to A2. Signs of effusion/synovitis may be positively associated with neuropathic-like pain and pain sensitivity. There are indications of a possible positive association between serum CRP levels and pain sensitivity. Given the quality and the small amount of included studies, uncertainty remains. Future studies with adequate sample size and follow-up are needed to strengthen the level of evidence.PROSPERO registration number: CRD42022329245.

Structural ultrasound of joints and tendons in healthy children: development of normative data.

BACKGROUND: Musculoskeletal ultrasound is a well accessible technique to assess disease activity in children with juvenile idiopathic arthritis. Knowledge of reference values of joint structures is indispensable to differentiate between physiological and pathological finding. The aim of this study was to assess the structural sonographic features of joints and tendons in healthy children from several age groups (0.2-18 year), and develop a set of normative data. METHODS: Greyscale ultrasound was performed in 500 healthy children (age 0.2-18 years) according to a predefined scanning protocol (Additional file 1) including the shoulder, elbow, wrist, second metacarpophalangeal joint, hip, knee, ankle, and first metatarsophalangeal joint). Demographic data and values of cartilage thickness, tendon diameters, and the degree of capsular distention measured by bone-capsular distance (BCD) were collected. Differences according to the sex were assessed by unpaired t-test. Single and multiple regression analyses were performed between the ultrasound outcomes and covariates such as age, height, weight and body mass index. Growth charts and tables were developed with respect to age. Nonparametric quantile regression was applied using the R-packages quantreg and quantregGrowth. RESULTS: A total of 195 male and 305 female volunteers were included between the age of 0 and 18 years (mean age 8.9; range: 0.2-17.9 years). Cartilage diminished markedly as children aged, and cartilage of the boys was significantly thicker compared to the girls in all joints (p < 0.001). In addition, cartilage became thinner as children's height and weight increased (beta regression coefficients between - 0.27 and - 0.01, p < 0.0001). Capsular distention (i.e., BCD > 0 mm) was uncommon in the ankle, wrist and MCP2 (resp. in 3, 6, and 3% of cases). It was more common in the suprapatellar and parapatellar knee, MTP1 and posterior recess of the elbow (resp. in 34, 32, 46, and 39% of cases). In the hip, some capsular distention was always present. Age was found to be the best predictor for BCD (beta regression coefficients between 0.05 and 0.13, p < 0.0001). Height was, in addition to age, a good predictor of tendon diameter (beta regression coefficients between 0.03 and 0.14, p < 0.0001). Growth curves and tables for each variable were developed. CONCLUSIONS: Reference values of sonographic cartilage thickness, BCD and diameters of tendons at several joints were established from 500 healthy children, aged between 0.2 and 18 years. Growth charts and tables were developed to distinguish normal findings from pathology in children with complaints suspicious of arthritis.

Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification.

BACKGROUND: Adalimumab blocks the action of tumor necrosis factor-α and reduces disease progression in rheumatoid arthritis and psoriatic arthritis. The effects of adalimumab in controlling progression of structural damage in erosive hand osteoarthritis (HOA) were assessed. METHODS: Sixty patients with erosive HOA on radiology received 40 mg adalimumab or placebo subcutaneously every two weeks during a 12-month randomized double-blind trial. Response was defined as the reduction in progression of structural damage according to the categorical anatomic phase scoring system. Furthermore, subchondral bone, bone plate erosion, and joint-space narrowing were scored according to the continuous Ghent University Score System (GUSSTM). RESULTS: The disease appeared to be active since 40.0% and 26,7% of patients out of the placebo and adalimumab group, respectively, showed at least one new interphalangeal (IP) joint that became erosive during the 12 months follow-up. These differences were not significant and the overall results showed no effect of adalimumab. Risk factors for progression were then identified and the presence of palpable soft tissue swelling at baseline was recognized as the strongest predictor for erosive progression. In this subpopulation at risk, statistically significant less erosive evolution on the radiological image (3.7%) was seen in the adalimumab treated group compared to the placebo group (14.5%) (P = 0.009). GUSSTM scoring confirmed a less rapid rate of mean increase in the erosion scores during the first 6 months of treatment in patients in adalimumab-treated patients. CONCLUSION: Palpable soft tissue swelling in IP joints in patients with erosive HOA is a strong predictor for erosive progression. In these joints adalimumab significantly halted the progression of joint damage compared to placebo.

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.

Development of radiographic classification criteria for hand osteoarthritis: a methodological report (Phase 2).

OBJECTIVES: In Phase 1 of developing new hand osteoarthritis (OA) classification criteria, features associated with hand OA were identified in a population with hand complaints. Radiographic findings could better discriminate patients with hand OA and controls than clinical examination findings. The objective of Phase 2 was to achieve consensus on the features and their weights to be included in three radiographic criteria sets of overall hand OA, interphalangeal OA and thumb base OA. METHODS: Multidisciplinary, international expert panels were convened. Patient vignettes were used to identify important features consistent with hand OA. A consensus-based decision analysis approach implemented using 1000minds software was applied to identify the most important features and their relative importance influencing the likelihood of symptoms being due to hand OA. Analyses were repeated for interphalangeal and thumb base OA. The reliability and validity of the proposed criteria sets were tested. RESULTS: The experts agreed that the criteria sets should be applied in a population with pain, aching or stiffness in hand joint(s) not explained by another disease or acute injury. In this setting, five additional criteria were considered important: age, morning stiffness, radiographic osteophytes, radiographic joint space narrowing and concordance between symptoms and radiographic findings. The reliability and validity were very good. CONCLUSION: Radiographic features were considered critical when determining whether a patient had symptoms due to hand OA. The consensus-based decision analysis approach in Phase 2 complemented the data-driven results from Phase 1, which will form the basis of the final classification criteria sets.

Blood transcriptomics to facilitate diagnosis and stratification in pediatric rheumatic diseases - a proof of concept study.

BACKGROUND: Transcriptome profiling of blood cells is an efficient tool to study the gene expression signatures of rheumatic diseases. This study aims to improve the early diagnosis of pediatric rheumatic diseases by investigating patients' blood gene expression and applying machine learning on the transcriptome data to develop predictive models. METHODS: RNA sequencing was performed on whole blood collected from children with rheumatic diseases. Random Forest classification models were developed based on the transcriptome data of 48 rheumatic patients, 46 children with viral infection, and 35 controls to classify different disease groups. The performance of these classifiers was evaluated by leave-one-out cross-validation. Analyses of differentially expressed genes (DEG), gene ontology (GO), and interferon-stimulated gene (ISG) score were also conducted. RESULTS: Our first classifier could differentiate pediatric rheumatic patients from controls and infection cases with high area-under-the-curve (AUC) values (AUC = 0.8 ± 0.1 and 0.7 ± 0.1, respectively). Three other classifiers could distinguish chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), and interferonopathies (IFN) from control and infection cases with AUC ≥ 0.8. DEG and GO analyses reveal that the pathophysiology of CRMO, IFN, and JIA involves innate immune responses including myeloid leukocyte and granulocyte activation, neutrophil activation and degranulation. IFN is specifically mediated by antibacterial and antifungal defense responses, CRMO by cellular response to cytokine, and JIA by cellular response to chemical stimulus. IFN patients particularly had the highest mean ISG score among all disease groups. CONCLUSION: Our data show that blood transcriptomics combined with machine learning is a promising diagnostic tool for pediatric rheumatic diseases and may assist physicians in making data-driven and patient-specific decisions in clinical practice.

Reliability and construct validity of ultrasonography of soft tissue and destructive changes in erosive osteoarthritis of the interphalangeal finger joints: a comparison with MRI.

OBJECTIVES: To study the reliability and construct validity of ultrasound in interphalangeal finger joints affected by erosive osteoarthritis (EOA) and non-EOA with MRI as the reference method. METHODS: 252 joints were examined by ultrasound, conventional radiography and clinical examination. Ultrasound was performed using a high-frequency linear transducer (12 × 18 MHz). On the same day, magnetic resonance images of 112 joints were obtained on a 3.0 T magnetic resonance unit. The ultrasound and MRI images were re-read independently by other readers unaware of the diagnosis, clinical and other imaging findings. Interobserver reliability was calculated by the percentage of exact agreement obtained and κ statistics. With MRI as the reference method, the sensitivity and specificity of ultrasound in detecting structural (bone erosions and osteophytes) and soft tissue (effusion and grey-scale synovitis) changes in EOA were calculated. RESULTS: Ultrasound and MRI were found to be more sensitive in detecting erosions than conventional radiography in EOA. A high agreement between ultrasound and MRI in the assessment of bone erosions (77.7%), osteophytes (75.9%) and synovitis (86.5%) was present. A high percentage of inflammatory changes was found in EOA, and in smaller amount in non-EOA, both confirmed by MRI. Good interobserver reliability of ultrasound was obtained for all variables (all median κ > 0.8). CONCLUSION: Grey-scale ultrasound proved to be a reliable and valid imaging technique to assess erosions and soft tissue changes, compared with MRI as a reference method in EOA.

Methotrexate treatment in hand osteoarthritis refractory to usual treatments: A randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To examine the effect of methotrexate (MTX) on pain and structural progression in symptomatic erosive hand osteoarthritis (HOA). METHODS: This 1-year prospective, single-centre, randomised, double-blind, placebo-controlled study (www.ClinicalTrial.gov, NCT01068405) followed up patients with symptomatic erosive HOA. Patients were randomised into two groups based on the drug that was administered: 10 mg methotrexate (MTX) per week or a placebo. The primary endpoint was the change in pain (determined using a visual analogue scale [VAS]) from baseline to 3 months. The secondary endpoints were pain VAS score at 12 months, clinical features (pain VAS score and function), radiographic features (the anatomical radiographic Verbruggen-Veys [VV] score and Gent University Score System), and magnetic resonance imaging (MRI) at 12 months. RESULTS: Sixty-four patients with HOA were randomised into either the placebo or MTX group. At 3 months, there was no significant difference in the mean decrease in the pain VAS score (mm) (MTX: 21.1 [standard deviation, 27.4], placebo: 11.7 [24.3]; p = 0.2). At 12 months, according to the VV score, erosive joints progressed significantly more to a remodelling phase in the MTX group than in the placebo group (27% vs 15%; p = 0.03). Joints with space loss appeared to be eroding less in the MTX group compared to the placebo group (8% vs 29%; p = 0.2). Synovitis on MRI at baseline could be associated with the erosive structural evolution of non-erosive joints (p = 0.02). CONCLUSIONS: Weekly doses of 10-mg MTX showed no superiority over the placebo in terms of pain relief at 3 or 12 months. CLINICAL TRIAL REGISTRATION NUMBER: This study was registered at www.ClinicalTrial.gov (NCT01068405).

Core outcome measurement instrument selection for physical function in hand osteoarthritis using the OMERACT Filter 2.1 process.

OBJECTIVE: Physical function is one of the Outcome Measures in Rheumatology (OMERACT) core outcome domains for hand osteoarthritis studies. Our aim was to select appropriate instrument(s) to measure this domain, as part of the development of a core outcome measurement set. METHODS: Following the OMERACT Filter 2.1 instrument selection process, the (function subscale of) the Australian/Canadian Hand Osteoarthritis Index (AUSCAN), Functional Index for Hand Osteoarthritis (FIHOA) and Michigan Hand Outcomes Questionnaire (MHQ) were assessed for domain match, feasibility, truth and discrimination. Data gathered from available literature, working group and patient surveys, and additional analyses in two hand osteoarthritis cohorts were used to inform a consensus process. Results were summarized in Summary of Measurements Properties tables and reviewed by the OMERACT technical advisory group. RESULTS: MHQ passed the assessment of domain match and feasibility by the working group and patient research partners. For AUSCAN important limitations in feasibility were noted, but domain match was good. FIHOA did not pass the assessment and was not taken through the follow-up assessment. Based on published literature, reliability and construct/longitudinal validity of both MHQ and AUSCAN fulfilled OMERACT standards. While clinical trial discrimination and thresholds of meaning were good for AUSCAN, results for MHQ were ambiguous. CONCLUSION: MHQ was provisionally endorsed as OMERACT core outcome measure for the core domain physical function. While AUSCAN may have better metric properties than MHQ, it received provisional endorsement as a second measure of function due to important feasibility issues. A research agenda to merit full endorsement was set.