MRI and ultrasonography for detection of early interphalangeal osteoarthritis.

OBJECTIVES: To assess the interest of MRI and ultrasonography (US) in identifying early and advanced interphalangeal (IP) OA. METHODS: We conducted a case-control study including patients with symptomatic hand OA (n=33) and young healthy volunteers (n=26). Proximal and distal IP joints were graded according to Kellgren and Lawrence (KL) grades. In OA patients, we separated IP joints into 2 groups: "at risk of OA" joints (potential early pre-radiographic OA joints, KL=0) and OA joints (KL=2-4). All IP joints from healthy participants were KL=0 and were considered strictly normal IP joints. Concurrently, synovitis, effusion, erosions, osteophytes, bone marrow lesions, cysts and cartilage space loss were graded by MRI and/or US. We assessed their prevalence, severity and diagnostic performance in hand OA and then compared normal IP joints from healthy participants and "at risk of OA" IP joints from OA patients as well as "at risk of OA" and OA IP joints from OA patients. RESULTS: The prevalence and grade of most MRI/US-detected lesions were higher in IP joints from OA patients than healthy participants. Except for osteophyte assessment, MRI seemed more sensitive than US. We found more MRI/US-detected lesions in "at risk of OA" IP joints than normal joints but also in OA than "at risk of OA" joints from OA patients. US appeared both sensitive and specific for detecting osteophytes in joints without radiographic abnormalities. CONCLUSIONS: MRI and US give good performance for detecting radiographic and pre-radiographic OA lesions and could be interesting tools to identify early hand OA.

Atlas of the OMERACT Heel Enthesitis MRI Scoring System (HEMRIS).

OBJECTIVE: Assessment of enthesitis, a key feature in spondyloarthritis (SpA) and psoriatic arthritis (PsA), using objective and sensitive methods is pivotal in clinical trials. MRI allows detection of both soft tissue and intra-osseous changes of enthesitis. This article presents an atlas for the Outcome Measures in Rheumatology (OMERACT) Heel Enthesitis Magnetic Resonance ImagingMRI Scoring System (HEMRIS). METHODS: Following a preliminary selection of potential examples of each grade, as per HEMRIS definitions, the images along with detailed definitions and reader rules were discussed at web-based, interactive meetings between the members of the OMERACT MRI in Arthritis Working Group. RESULTS: Reference images of each grade of the MRI features to be assessed using HEMRIS, along with reader rules and recommended MRI sequences are depicted. CONCLUSION: The presented reference images can be used to guide scoring Achilles tendon and plantar fascia (plantar aponeurosis) enthesitis according to the OMERACT HEMRIS in clinical trials and cohorts in which MRI enthesitis is used as an outcome.

Reliability of a consensus-based ultrasound definition and scoring for enthesitis in spondyloarthritis and psoriatic arthritis: an OMERACT US initiative.

OBJECTIVES: To evaluate the reliability of consensus-based ultrasound (US) definitions of elementary components of enthesitis in spondyloarthritis (SpA) and psoriatic arthritis (PsA) and to evaluate which of them had the highest contribution to defining and scoring enthesitis. METHODS: Eleven sonographers evaluated 40 entheses from five patients with SpA/PsA at four bilateral sites. Nine US elementary lesions were binary-scored: hypoechogenicity, thickened insertion, enthesophytes, calcifications, erosions, bone irregularities, bursitis and Doppler signal inside and around enthesis. Kappa statistics were used to evaluate reliability. Sonographers were also asked to state which lesions can be considered as inflammatory or structural and should be included in the final definition of enthesitis. Only the lesions, scored as present in at least 75% of the entheses considered as having an enthesitis, were included in the final definition. RESULTS: The prevalence of detected lesions was quite low except for enthesophytes (55%) and bone irregularities (54%). Reliability ranged from poor to good (the lowest for thickened enthesis (kappa 0.1 (95% CI 0 to 0.7)) and the highest for enthesophytes (kappa 0.6 (95% CI 0.5 to 0.7)). When adjusted for low prevalence, kappa values increased for all lesions, with the best result observed for detecting Doppler signal at insertion (0.9) and for bursitis (0.8). The US components included in the final definition were hypoechogenicity, increased thickness at enthesis, erosions and calcifications/enthesophytes and Doppler signal at insertion. CONCLUSION: By using a consensus-based stepwise approach, a final reliable US score and definition of enthesitis in SpA/PsA were produced. Further studies are sought for implementing this score in clinical trials and practice.

Sustainability of TNF-blocker tapering in rheumatoid arthritis over 3 years: long-term follow-up of the STRASS (Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study) randomised controlled trial.

INTRODUCTION: We have limited data on the sustainability of tumour necrosis factor (TNF)-blocker tapering in rheumatoid arthritis (RA) in remission over the long term in real-life settings. This study aimed to assess the probability of sustained dose reduction of TNF-blockers in an observational 3-year extended follow-up of the Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study (STRASS), a randomised controlled trial comparing progressive TNF-blocker injections (spacing arm (S-arm) to maintenance arm (M-arm)) in patients with RA in stable remission. METHODS: In 2015, clinical data for the completer population were retrospectively collected at 1, 2 and 3 years after the end of the trial. The endpoints were the proportion of patients free of a biological disease-modifying antirheumatic drug (bDMARD) treatment, a sustainably spaced injection of TNF-blockers and a full-dose regimen as well as the mean dose of bDMARD intake and treatment switch rate. RESULTS: Overall, 96 patients (76.8% of the completers) had data available up to 3 years; 11.5% discontinued TNF-blockers (5.8% vs 18.2% in the M-arm and S-arm, p=0.06), 30.2% had a tapered regimen (28.8% vs 31.8%, p=0.76) and 37.5% retained a full dose (44.2% vs 29.5%, p=0.14). The mean TNF-blocker dose quotient was 66% of the full dose (74% vs 58% in the M-arm and S-arm, p=0.06); 20.8% switched to another bDMARD (21.2% vs 20.5%, p=0.94). CONCLUSION: Sustained TNF-blocker de-escalation or withdrawal is achievable in 41% of patients over 3 years with limited dose reduction. Optimal strategies remain to be determined to maintain remission after TNF-blocker tapering or discontinuation.

Development and Reliability of the OMERACT Thumb Base Osteoarthritis Magnetic Resonance Imaging Scoring System.

OBJECTIVE: To develop the Outcome Measures in Rheumatology (OMERACT) thumb base osteoarthritis (OA) magnetic resonance imaging (MRI) scoring system (TOMS) for the assessment of inflammatory and structural abnormalities in this hand OA subset, and test its cross-sectional reliability. METHODS: Included features and their scaling were agreed upon by members of the OMERACT MRI Task Force using the Hand OA MRI scoring system as a template. A reliability exercise was performed in which 3 readers participated, using a preliminary atlas with examples to facilitate reading. Each reader independently scored a set of 20 MRI (coronal and axial T1- and T2-weighted fat-suppressed images, of which 5 included T1-weighted fat-suppressed post-Gadolinium images). Intra- and inter-reader reliability were assessed using ICC, percentage exact agreement (PEA), and percentage close agreement (PCA). RESULTS: The TOMS assessed the first carpometacarpal (CMC-1) and scaphotrapeziotrapezoid (STT) joints for synovitis, subchondral bone defects (including erosions, cysts, and bone attrition), osteophytes, cartilage, and bone marrow lesions on a 0-3 scale (normal to severe). Subluxation was evaluated only in the CMC-1 joint (absent/present). Reliability of scoring for both joints was comparable. Interreader ICC were good for all features (0.77-0.99 and 0.74-0.96 for CMC-1 and STT joints, respectively). Intrareader reliability analyses gave similar results. PCA was ≥ 65% for all features. PEA was low to moderate, with better performance for subchondral bone defects, subluxation, and bone marrow lesions. CONCLUSION: A thumb base OA MRI scoring system has been developed. The OMERACT TOMS demonstrated good intrareader and interreader reliability. Longitudinal studies are warranted to investigate reliability of change scores and responsiveness.

MRI and serum biomarkers correlate with radiographic features in painful hand osteoarthritis.

OBJECTIVES: To explore the relationship between clinical findings, biologic biomarkers, conventional radiography and MRI in patients with painful hand OA. METHODS: The following patient baseline data from the DORA study (evaluating anti-TNF-α agents against painful hand OA) were used: clinical assessment (pain, swelling, stiffness and function: Dreiser functional hand index [FIHOA] and Cochin hand functional scale [CHFS]); measurement of biomarkers (cartilage oligomeric matrix protein (COMP), type IIA collagen N-propeptid (PIINP), hyaluronic acid (HA), ultrasensitive C-reactive protein (usCRP), tumour necrosis factor (TNF), interleukin (IL)-6, IL-1ß and urinary CTXII); radiological staging (Verbruggen, Kallman, Kellgren-Lawrence); anatomical evaluation by contrast-enhanced MRI of proximal and distal interphalangeal joints of dominant hand. Associations between clinical, biomarker and imaging findings were assessed using the Spearman correlation coefficient and test. RESULTS: 18 patients were recruited, and 144 joints studied. A correlation was found between clinical features (pain, FIHOA, CHFS) and the Verbruggen score (respectively: p=0.05, r=0.47; p=0.05, r=0.48; p=0.05, r=0.48). Serum IL-1 level was strongly associated with loss of function (FIHOA: p=0.02, r=-0.73; CHFS: p=0.01, r=-0.76) and radiological erosions (p=0.03, r=0.7) as with urinary CTX2. A significant association was found between MRI osteophytes and usCRP (p=0.0026). MRI and radiological features were significantly correlated except for synovitis and bone marrow lesions. CONCLUSIONS: MRI synovitis was not correlated with radiological scores, clinical or biologic markers of inflammation. There was a strong correlation between other MRI features and radiological scores. Serum IL-1 level was associated with structural damage and function.

Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial (STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study).

UNLABELLED: Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission. OBJECTIVE: The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission. METHODS: The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%). RESULTS: 64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression. CONCLUSIONS: Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41.

Validation of the OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) for the Hand and Foot in a Randomized Placebo-controlled Trial.

OBJECTIVE: To assess changes following treatment and the reliability and responsiveness to change of the Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) in a randomized controlled trial. METHODS: Forty patients with PsA randomized to either placebo or abatacept (ABA) had MRI of either 1 hand (n = 20) or 1 foot (n = 20) at baseline and after 6 months. Images were scored blindly twice by 3 independent readers according to the PsAMRIS (for synovitis, tenosynovitis, periarticular inflammation, bone edema, bone erosion, and bone proliferation). RESULTS: Inflammatory features improved numerically but statistically nonsignificantly in the ABA group but not the placebo group. Baseline intrareader intraclass correlation coefficients (ICC) were good (≥ 0.50) to very good (≥ 0.80) for all features in both hand and foot. Baseline interreader ICC were good (ICC 0.72-0.96) for all features, except periarticular inflammation and bone proliferation in the hand and tenosynovitis in the foot (ICC 0.25-0.44). Intrareader and interreader ICC for change scores varied. Guyatt's responsiveness index (GRI) was high for inflammatory features in the hand and metatarsophalangeal joints (GRI -0.67 to -3.13; bone edema not calculable). Minimal change and low prevalence resulted in low ICC and GRI for bone damage. CONCLUSION: PsAMRIS showed overall good intrareader agreement in the hand and foot, and inflammatory feature scores were responsive to change, suggesting that PsAMRIS may be a valid tool for MRI assessment of hands and feet in PsA clinical trials.

The Longitudinal Reliability and Responsiveness of the OMERACT Hand Osteoarthritis Magnetic Resonance Imaging Scoring System (HOAMRIS).

OBJECTIVE: To evaluate the interreader reliability of change scores and the responsiveness of the OMERACT Hand Osteoarthritis (OA) Magnetic Resonance Image (MRI) Scoring System (HOAMRIS). METHODS: Paired MRI (baseline and 5-yr followup) from 20 patients with hand OA were scored with known time sequence by 3 readers according to the HOAMRIS: Synovitis, erosive damage, cysts, osteophytes, cartilage space loss, malalignment, and bone marrow lesions (BML; 0-3 scales with 0.5 increments for synovitis, erosive damage, and BML). Interreader reliability for status and change scores were assessed by intraclass correlation coefficients (ICC), percentage exact agreement and percentage close agreement (PEA/PCA), and smallest detectable change (SDC). Responsiveness was assessed by standardized response means (SRM). RESULTS: Cross-sectional interreader ICC were good to very good (≥ 0.74) for all features except synovitis, cysts, and malalignment (ICC 0.50-0.58). The range of change values was small, leading to low ICC for change scores. The SDC values for sum scores (total range 0-24) varied between 1.97-3.05 (except 1.08 for malalignment). For status scores, PEA/PCA on scores in individual joints across the readers were 8.1-50.0 and 43.8-78.1, respectively. Similarly, PEA/PCA for change scores were 20.6-63.8 and 66.3-93.1, respectively. All features except cysts and BML demonstrated good responsiveness with higher SRM for sum scores (range 0.46-1.62) than for scores in individual joints (range 0.24-0.73). CONCLUSION: Good to very good interreader ICC values were found for cross-sectional readings, whereas the longitudinal reliability was lower because of a smaller range of change scores. All features, except cysts and BML, showed good responsiveness.

The OMERACT MRI in Arthritis Working Group - Update on Status and Future Research Priorities.

OBJECTIVE: To provide an update on the status and future research priorities of the Outcome Measures in Rheumatology (OMERACT) magnetic resonance imaging (MRI) in arthritis working group. METHODS: A summary is provided of the activities of the group within rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA), and its research priorities. RESULTS: The OMERACT RA MRI score (RAMRIS) evaluating bone erosion, bone edema (osteitis), and synovitis is now the standard method of quantifying articular pathology in RA trials. Cartilage loss is another important part of joint damage, and at the OMERACT 12 conference, we provided longitudinal data demonstrating reliability and sensitivity to change of the RAMRIS JSN component score, supporting its use in future clinical trials. The MRI group has previously developed a PsA MRI score (PsAMRIS). At OMERACT 12, PsAMRIS was evaluated in a randomized placebo-controlled trial of patients with PsA, demonstrating the responsiveness and discriminatory ability of applying the PsAMRIS to hands and feet. A hand OA MRI score (HOAMRIS) was introduced at OMERACT 11, and has subsequently been further validated. At OMERACT 12, good cross-sectional interreader reliability, but variable reliability of change scores, were reported. Potential future research areas were identified at the MRI session at OMERACT 12 including assessment of tenosynovitis in RA and enthesitis in PsA and focusing on alternative MRI techniques. CONCLUSION: MRI has been further developed and validated as an outcome measure in RA, PsA, and OA. The group will continue its efforts to optimize the value of MRI as a robust biomarker in rheumatology clinical trials.

Iterative development and reliability of the OMERACT hand osteoarthritis MRI scoring system.

OBJECTIVE: To develop and test the interreader reliability of the OMERACT Hand Osteoarthritis Magnetic Resonance Scoring System (HOAMRIS) for assessment of structural and inflammatory hand OA features in the interphalangeal joints. METHODS: The HOAMRIS was developed through an iterative process. Selection of features and their scaling was agreed upon through consensus by members of the OMERACT Magnetic Resonance Imaging (MRI) Task Force, using the Oslo Hand Osteoarthritis (OA) MRI Score system as a template. Two reliability exercises were performed, in which 6 and 4 readers participated, respectively. After the first exercise, an atlas was developed and used in the second exercise to facilitate reading. In each exercise, readers independently scored 8 MRI scans from the Oslo Hand OA cohort (coronal/axial short-tau inversion recovery and coronal/axial/sagittal T1-weighted fat-suppressed pre-/post-Gadolinium images). Interreader reliability was assessed by intraclass correlation coefficients (ICC), percentage exact and close agreement (PEA/PCA). RESULTS: The preliminary OMERACT HOAMRIS included assessment of synovitis, erosive damage, cysts, osteophytes, cartilage space loss, malalignment, and bone marrow lesions (BML), of which all were scored on a 0-3 scale for normal, mild, moderate, and severe (increments of 0.5 for synovitis, erosive damage, and BML). In the first exercise, most features showed good to very good ICC values (0.64-0.94), except synovitis (0.34). In the second exercise using the atlas, the ICC values were > 0.74 for all MRI features, and the PEA/PCA values were higher than in the first exercise. CONCLUSION: A preliminary HOAMRIS with good to very good interreader reliability was developed. Longitudinal studies are needed to assess its sensitivity to change.

The OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) is reliable and sensitive to change: results from an OMERACT workshop.

OBJECTIVE: The aim of this multireader exercise was to assess the reliability and sensitivity to change of the psoriatic arthritis magnetic resonance imaging score (PsAMRIS) in PsA patients followed for 1 year. METHODS: MRI was acquired from 12 patients with PsA before initiation of treatment and after 12 months. MR images were scored according to PsAMRIS (for synovitis, tenosynovitis, periarticular inflammation, bone marrow edema, bone erosion, and bone proliferation) under standardized conditions, in unknown chronological order. Intraobserver/interobserver reliability was examined by intraclass correlation coefficients (ICC) and sensitivity to change by standardized response means (SRM). RESULTS: The interobserver reliability of PsAMRIS was high for synovitis, tenosynovitis, periarticular inflammation, and bone edema status and change scores (interobserver ICC 0.87-0.97). The intraobserver reliability was moderate to high (ICC 0.60-0.98) for status and change scores, except for change in periarticular inflammation (ICC 0.33). PsAMRIS sensitivity to change was moderate for synovitis, tenosynovitis, and periarticular inflammation (SRM 0.5-0.8), while poor (SRM 0.1-0.3) for bone marrow edema, erosion, and bone proliferation. Rare occurrence and minimal change contributed to poor SRM and change-score ICC for bone parameters. CONCLUSION: This multireader exercise, performed under standardized conditions, confirmed PsAMRIS to have high interobserver and intraobserver reliability for hand PsA. Measures of inflammation were sensitive to change, implying that PsAMRIS may be a valuable tool for monitoring change in inflammation during PsA clinical trials.

Update on research and future directions of the OMERACT MRI inflammatory arthritis group.

The OMERACT Magnetic Resonance Imaging (MRI) Task Force has developed and evolved the psoriatic arthritis MRI score (PsAMRIS) over the last few years, and at OMERACT 10, presented longitudinal evaluation by multiple readers, using PsA datasets obtained from extremity MRI magnets. Further evaluation of this score will require more PsA imaging datasets. As well, due to improved image resolution since the development of the original rheumatoid arthritis MRI scoring system (RAMRIS), the Task Force has worked on semiquantitative assessment of joint space narrowing, and developed a reliable method as a potential RAMRIS addendum, although responsiveness will need to be evaluated. One of the strengths of MRI is the ability to detect subclinical synovitis, so the group worked on obtaining low disease activity/clinical remission datasets from a number of international centers and presented cross-sectional findings. Subsequent longitudinal evaluation of this unique resource will be a major continuing focus for the group.

Human NK cells display major phenotypic and functional changes over the life span.

Aging is generally associated with an increased predisposition to infectious diseases and cancers, related in part to the development of immune senescence, a process that affects all cell compartments of the immune system. Although many studies have investigated the effects of age on natural killer (NK) cells, their conclusions remain controversial because the diverse health status of study subjects resulted in discordant findings. To clarify this situation, we conducted the first extensive phenotypic and functional analysis of NK cells from healthy subjects, comparing NK cells derived from newborn (cord blood), middle-aged (18-60 years), old (60-80 years), and very old (80-100 years) subjects. We found that NK cells in cord blood displayed specific features associated with immaturity, including poor expression of KIR and LIR-1/ILT-2 and high expression of both NKG2A and IFN-gamma. NK cells from older subjects, on the other hand, preserved their major phenotypic and functional characteristics, but with their mature features accentuated. These include a profound decline of the CD56(bright) subset, a specific increase in LIR-1/ILT-2, and a perfect recovering of NK-cell function following IL2-activation in very old subjects. We conclude that the preservation of NK cell features until very advanced age may contribute to longevity and successful aging.

The OMERACT MRI inflammatory arthritis group: advances and future research priorities.

The OMERACT magnetic resonance imaging (MRI) in inflammatory arthritis group previously developed the rheumatoid arthritis MRI score (RAMRIS) for use in clinical studies, evaluated the use of extremity MRI, and initiated development of a psoriatic arthritis MRI score (PsAMRIS). At OMERACT 9 the group looked at clarifications of applying the RAMRIS, and presented data from a study examining how the contrast agent gadolinium affects RAMRIS outcomes. Much of the group's effort has been aimed at the iterative development of its PsA score, and reported exercises examining this score demonstrated encouraging results, allowing subsequent presentation of a preliminary PsAMRIS. The large amount of data presented were followed by discussions with the wider audience highlighting constructive suggestions for future research priorities, including further feasibility studies, understanding imaging remission, and further improvements to PsAMRIS.

Testing an OMERACT MRI scoring system for peripheral psoriatic arthritis in cross-sectional and longitudinal settings.

OBJECTIVE: Magnetic resonance imaging (MRI) is increasingly used to measure articular inflammation and damage in patients with psoriatic arthritis (PsA). We evaluated the reliability of a new OMERACT PsA MRI scoring system, PsAMRIS, in PsA fingers. METHODS: In 2 separate studies, MRI scans were obtained from patients with clinical evidence of synovitis or dactylitis of the fingers. For the first cross-sectional study, images were obtained at one timepoint. For the second longitudinal study, images were obtained at 2 timepoints, 6 weeks apart. Scans were scored using PsAMRIS in an international multireader setting, for synovitis, tenosynovitis, periarticular inflammation, bone edema, bone erosions, and bone proliferation. RESULTS: Global status scores from both datasets revealed moderate to high reliability for scoring most features, although reliability was poor for periarticular inflammation in the cross-sectional study. Change scores that reflected inflammatory activity also exhibited moderate to good reliability in the longitudinal exercise, despite there being very little absolute change in MRI synovitis or tenosynovitis observed in this dataset. At the distal interphalangeal joints, reliability for change scores was acceptable only for synovitis and tenosynovitis. CONCLUSION: Further development and testing of the PsAMRIS is planned to improve its performance as a clinical and research tool to identify and measure pathology in peripheral joint PsA.

The OMERACT psoriatic arthritis magnetic resonance imaging scoring system (PsAMRIS): definitions of key pathologies, suggested MRI sequences, and preliminary scoring system for PsA Hands.

This article describes a preliminary OMERACT psoriatic arthritis magnetic resonance image scoring system (PsAMRIS) for evaluation of inflammatory and destructive changes in PsA hands, which was developed by the international OMERACT MRI in inflammatory arthritis group. MRI definitions of important pathologies in peripheral PsA and suggestions concerning appropriate MRI sequences for use in PsA hands are also provided.