Peripheral and Central Sensitization of Pain in Individuals With Hand Osteoarthritis and Associations With Self-Reported Pain Severity.

OBJECTIVE: Pain sensitization, an important osteoarthritis (OA) pain mechanism, has not been substantially investigated in patients with hand OA. It is unknown how peripheral and central sensitization are related to self-reported hand pain. METHODS: Individuals with verified hand OA in the Nor-Hand study underwent quantitative sensory testing of pressure pain thresholds (PPTs) locally (painful and nonpainful finger joints) and remotely (wrist, trapezius, and tibialis anterior muscles), and testing of temporal summation (TS), a manifestation of central sensitization. We examined cross-sectional associations of PPT tertiles and TS with hand pain using the Numerical Rating Scale (NRS) (range 0-10) and the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subscale (range 0-20). Linear regression models were adjusted for demographics, psychosocial factors, and radiographic severity. RESULTS: This study included 282 participants (88% female) with a median age of 61 years (interquartile range [IQR] 57-66). Participants with the lowest PPTs in their finger joints and in most remote locations reported higher NRS pain values, compared to patients with the highest PPTs, with adjusted ß values ranging from 0.6 (95% confidence interval [95% CI] 0.0, 1.2) to 0.9 (95% CI 0.3, 1.5). The 118 participants (42%) with TS reported higher mean ± SD NRS pain values compared to those without TS (4.1 ± 2.4 versus 3.1 ± 1.7; adjusted ß = 0.6 [95% CI 0.2, 1.1]). Neither PPTs nor the presence of TS were associated with AUSCAN pain. CONCLUSION: Central sensitization was common in patients with hand OA. Lower local and widespread PPTs and the presence of TS were associated with higher hand pain intensity, even after adjustment for demographics, psychosocial factors, and radiographic severity. Sensitization may therefore represent a possible treatment target.

Comparing the disease course of patients with seronegative and seropositive rheumatoid arthritis fulfilling the 2010 ACR/EULAR classification criteria in a treat-to-target setting: 2-year data from the ARCTIC trial.

OBJECTIVES: Recent studies suggest that implementation of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) leads to higher inflammatory activity in seronegative compared with seropositive patients at time of diagnosis. Our aim was to compare the disease course in seronegative and seropositive patients classified according to the 2010 criteria. METHODS: DMARD-naïve patients with RA fulfilling the 2010 criteria were included in the treat-to-target ARCTIC trial and followed for 24 months. We stratified patients as seropositive (rheumatoid factor (RF)+, anticitrullinated protein antibodies (ACPA)+ or both) or seronegative (RF- and ACPA-) and compared disease activity, radiographic progression, treatment response and remission rates across groups. RESULTS: 230 patients were included with mean (SD) age 51.4 (13.7) years, and 61% were female. 34 patients (15%) were seronegative. At 24 months, disease activity measures, radiographic progression and remission rates were similar between groups, despite more inflammatory activity in seronegative patients at baseline. Treatment response was slower in seronegative compared with seropositive patients. The groups received similar treatment. CONCLUSION: Our findings suggest that among patients with RA classified according to the 2010 ACR/EULAR criteria, seronegative patients respond well to modern treatment strategies. However, treatment response was somewhat slower in seronegative patients and radiographic progression was similar in seronegative and seropositive patients. Our results indicate that seronegative RA is not a mild form of the disease and requires intensive treat-to-target therapy similar to treatment of seropositive RA.

DAPSA and ultrasound show different perspectives of psoriatic arthritis disease activity: results from a 12-month longitudinal observational study in patients starting treatment with biological disease-modifying antirheumatic drugs.

OBJECTIVES: Disease Activity index for PSoriatic Arthritis (DAPSA) (sum score 68/66 tender/swollen joint counts (68TJC/66SJC), patient's global assessment, pain and C-reactive protein (CRP)) is recommended for clinical assessment of disease activity in patients with psoriatic arthritis (PsA). Ultrasound (US) (grey scale (GS) and power Doppler (PD)) detects inflammation in joints and extra-articular structures. The present objectives were to explore the longitudinal relationships between DAPSA, clinical assessment as well as patient-reported outcome measures (PROMs) with US in patients with PsA initiating biological DMARDs and the associations between DAPSA and US remission. METHODS: 47 patients with PsA were examined at baseline and after 3, 6, 9 and 12 months. Assessments included 68TJC/66SJC, examiner's global assessment (EGA), PROMs, CRP, erythrocyte sedimentation rate (ESR) and US GS and PD (48 joints, 10 flexor tendons, 14 entheses, 4 bursae). Clinical composite scores and PD sum scores (0=remission) were calculated. Longitudinal associations were explored by generalised estimating equations with linear and logistic regression. RESULTS: DAPSA was not longitudinally associated to PD. 66SJC, ESR, 28-joint Disease Activity Score, EGA and CRP were longitudinally associated with PD (p<0.001-0.03), whereas the pain-related components of DAPSA (68TJC and pain) as well as PROMs were not associated. At 6-12 months, remission was achieved in 29%-33 % of the patients for DAPSA and 59%-70 % for PD. The association between DAPSA and PD remission was not significant (p=0.33). CONCLUSIONS: DAPSA was not associated with US inflammatory findings which indicates that DAPSA and US may assess different aspects of PsA activity.

Ultrasound-detected osteophytes predict the development of radiographic and clinical features of hand osteoarthritis in the same finger joints 5 years later.

BACKGROUND: Structural pathology may be present in joints without radiographic evidence of osteoarthritis (OA). Ultrasound is a sensitive tool for early detection of osteophytes. Our aim was to explore whether ultrasound-detected osteophytes (in radiographically and clinically normal finger joints) predicted the development of radiographic and clinical hand OA 5 years later. METHODS: We included finger joints without radiographic OA (Kellgren-Lawrence grade (KLG)=0; n=301) or no clinical bony enlargements (n=717) at baseline and examined whether ultrasound-detected osteophytes predicted incident radiographic OA (KLG ≥1, osteophytes or joint space narrowing (JSN)) or incident clinical bony enlargement (dependent variables) in the same joints 5 years later. We applied logistic regression with generalised estimating equations adjusted for age, sex, body mass index and follow-up time. RESULTS: Ultrasound demonstrated osteophytes in 86/301 (28.6%) joints without radiographic OA and 392/717 (54.7%) joints without clinical bony enlargement. These osteophytes were confirmed in the majority of joints where MRI assessment was available. Significant associations were found between ultrasound-detected osteophytes and development of both radiographic OA (OR=4.1, 95% CI 2.0 to 8.1) and clinical bony enlargement (OR=3.5, 95% CI 2.4 to 5.1) and also incident radiographic osteophytes (OR=4.2, 95% CI 2.1 to 8.5) and JSN (OR=5.3, 95% CI 2.1 to 13.4). CONCLUSION: Ultrasound-detected osteophytes predicted incident radiographic and clinical hand OA 5 years later. These results support the use of ultrasound for early detection of OA.

Exploring a new ultrasound score as a clinical predictive tool in patients with rheumatoid arthritis starting abatacept: results from the APPRAISE study.

OBJECTIVES: To explore whether changes in a composite (power Doppler/greyscale ultrasound (PDUS)) synovitis score, developed by the OMERACT-EULAR-Ultrasound Task Force, predict disease activity outcomes in rheumatoid arthritis (RA). METHODS: Patients with RA who were methotrexate inadequate responders starting abatacept were evaluated. Individual joint PDUS scores were combined in the Global OMERACT-EULAR Synovitis Score (GLOESS) for metacarpophalangeal joints (MCPs) 2-5, all joints (22 paired) and a reduced (9 paired) joint set. The predictive value of changes in GLOESS at week 1-16 evaluations for clinical status and response (Disease Activity Score (DAS)28 (C reactive protein, CRP) <2.6; DAS28(CRP) ≤3.2; DAS28(CRP) ≥1.2 improvement) up to week 24, and correlations between DAS28 and GLOESS were assessed. RESULTS: Eighty-nine patients completed the 24-week treatment period. Changes in GLOESS (MCPs 2-5) from weeks 1 to 16 were unable to predict DAS28 outcomes up to week 24. However, significant improvements in GLOESS (MCPs 2-5) were observed at week 12 in patients with DAS28 ≥1.2 improvement at week 24 versus those who did not achieve that clinical response. In patients achieving DAS28 ≥1.2 improvement or DAS28 ≤3.2 at week 24, changes in GLOESS (22 and 9 paired joint sets) were greater in patients who already achieved DAS28 ≥1.2 at week 12 than in those who did not. No significant correlations were found between changes in DAS28 and GLOESS definitions at any time point. CONCLUSIONS: PDUS was not correlated with clinical status or response as measured by DAS28-derived criteria, and PDUS changes were not predictive of clinical outcome. The discrepancies require further exploration. TRIAL REGISTRATION NUMBER: NCT00767325; Results.

EFSUMB COMPASS for Rheumatologists dissemination and implementation--an international survey.

AIM: The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) competency assessment (COMPASS) for rheumatologists performing musculoskeletal ultrasound (MSUS) was developed and published 2 years ago. It consists of a 3 level competency system. The objective of this study was to evaluate how the EFSUMB COMPASS has been disseminated and implemented and to assess the potential obstacles encountered. MATERIALS AND METHODS: A questionnaire was developed and distributed by e-mail to all rheumatologists certified as EFSUMB level 3. RESULTS: Seventeen (85%) rheumatologists considered that the EFSUMB COMPASS is useful for training MSUS. The majority of them (17; 85%) had informed their colleagues or national rheumatology societies about the EFSUMB COMPASS. The most common obstacle encountered for the implementation of the COMPASS was the lack of time for supervision of the trainees (9; 45%). A total of 83 rheumatologists had been trained and assessed for competency in the three EFSUMB levels. CONCLUSION: This survey highlights the current status of EFSUMB COMPASS implementation in European countries with an expected increased number of rheumatologists being able to train and assess new trainees. Still, more efforts should be done for a higher implementation of EFSUMB COMPASS across European countries.

Development of a feasible and responsive ultrasound inflammation score for rheumatoid arthritis through a data-driven approach.

OBJECTIVE: To develop and validate a responsive and feasible ultrasound inflammation score for rheumatoid arthritis (RA). METHODS: We used data from cohorts of early RA (development) and established RA starting/switching biologic therapy (validation). 4 tendons and 36 joints were examined by a grey scale (GSUS) and power Doppler semiquantitative ultrasound (PDUS) scoring system (full score). Ultrasound score components were selected based on factor analyses of 3-month change in the development cohort. Responsiveness was assessed by standardised response means (SRMs). We assessed the proportion of information retained from the full score by linear regression. RESULTS: 118 patients with early and 212 patients with established RA were included. The final ultrasound score included 8 joints (metacarpophalangeal 1-2-3, proximal interphalangeal 2-3, radiocarpal, metatarsophalangeal 2-3) and 1 tendon (extensor carpi ulnaris) examined bilaterally. The 6-month SRMs for the final score were -1.24 (95% CI -1.47 to -1.02) for GSUS, and -1.09 (-1.25 to -0.92) for PDUS in early RA, with 87% of total information retained for GSUS and 90% for PDUS. The new score performed somewhat better than formerly proposed scores in the validation cohort. CONCLUSIONS: The Ultrasound in Rheumatoid Arthritis 9 joint/tendon score (USRA9) inflammation score showed good responsiveness, retained most of the information from the original full score and overall performed better than previous scores in a validation cohort. TRIAL REGISTRATION NUMBERS: NCT01205854, ACTRN12610000284066; Post-results.

Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study.

OBJECTIVES: To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). METHODS: In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology-European League Against Rheumatism (OMERACT-EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT-EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2-5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. RESULTS: Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2-5): -0.7 (95% CIs -1.2 to -0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. CONCLUSIONS: In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. TRIAL REGISTRATION NUMBER: NCT00767325.

Responsiveness in rheumatoid arthritis. a report from the OMERACT 11 ultrasound workshop.

OBJECTIVE: To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Task Force on the validity of different US measures in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) presented during the OMERACT 11 Workshop. METHODS: The Task Force is an international group aiming to iteratively improve the role of US in arthritis clinical trials. Recently a major focus of the group has been the assessment of responsiveness of a person-level US synovitis score in RA: the US Global Synovitis Score (US-GLOSS) combines synovial hypertrophy and power Doppler signal in a composite score detected at joint level. Work has also commenced examining assessment of tenosynovitis in RA and the role of US in JIA. RESULTS: The US-GLOSS was tested in a large RA cohort treated with biologic therapy. It showed early signs of improvement in synovitis starting at Day 7 and increasing to Month 6, and demonstrated sensitivity to change of the proposed grading. Subsequent voting questions concerning the application of the US-GLOSS were endorsed by > 80% of OMERACT delegates. A standardized US scoring system for detecting and grading severity of RA tenosynovitis and tendon damage has been developed, and acceptable reliability data were presented from a series of exercises. A preliminary consensus definition of US synovitis in pediatric arthritis has been developed and requires further testing. CONCLUSION: At OMERACT 11, consensus was achieved on the application of the US-GLOSS for evaluating synovitis in RA; and work continues on development of RA tenosynovitis scales as well as in JIA synovitis.