A Phase II Trial of Lutikizumab, an Anti–Interleukin‐1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis

Objective: To assess the efficacy and safety of the anti–interleukin‐1α/β (anti–IL‐1α/β) dual variable domain immunoglobulin lutikizumab (ABT‐981) in patients with knee osteoarthritis (OA) and evidence of synovitis. Methods: Patients (n = 350; 347 analyzed) with Kellgren/Lawrence grade 2–3 knee OA and synovitis (determined by magnetic resonance imaging [MRI] or ultrasound) were randomized to receive placebo or lutikizumab 25, 100, or 200 mg subcutaneously every 2 weeks for 50 weeks. The coprimary end points were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at week 16 and change from baseline in MRI‐assessed synovitis at week 26. Results: The WOMAC pain score at week 16 had improved significantly versus placebo with lutikizumab 100 mg (P = 0.050) but not with the 25 mg or 200 mg doses. Beyond week 16, the WOMAC pain score was reduced in all groups but was not significantly different between lutikizumab‐treated and placebo‐treated patients. Changes from baseline in MRI‐assessed synovitis at week 26 and other key symptom‐ and most structure‐related end points at weeks 26 and 52 were not significantly different between the lutikizumab and placebo groups. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumab versus placebo. Reductions in neutrophil and high‐sensitivity C‐reactive protein levels plateaued with lutikizumab 100 mg, with further reductions not observed with the 200 mg dose. Immunogenic response to lutikizumab did not meaningfully affect systemic lutikizumab concentrations. Conclusion: The limited improvement in the WOMAC pain score and the lack of synovitis improvement with lutikizumab, together with published results from trials of other IL‐1 inhibitors, suggest that IL‐1 inhibition is not an effective analgesic/antiinflammatory therapy in most patients with knee OA and associated synovitis

International consensus for ultrasound lesions in gout: Results of delphi process and web-reliability exercise

Objective. To produce consensus-based definitions of the US elementary lesions in gout and to test their reliability in a web-based exercise. Methods. The process consisted of two steps. In the first step a written Delphi questionnaire was developed from a systematic literature review and expert international consensus. This collated information resulted in four statements defining US elementary lesions: double contour (DC), tophus, aggregates and erosion. The Delphi questionnaire was sent to 35 rheumatology experts in US, asking them to rate their level of agreement or disagreement with each statement. The second step tested the reliability by a web-exercise. US images of both normal and gouty elementary lesions were collected by the participants. A facilitator then constructed an electronic database of 110 images. The database was sent to the participants, who evaluated the presence/absence of US elementary lesions. A group of 20 images was displayed twice to evaluate intra-reader reliability. Results. A total of 32 participants responded to the questionnaires. Good agreement (>80%) was obtained for US definitions on DC, tophus, aggregates and erosion in the Delphi exercise after three rounds. The reliability on images showed inter-reader κ values for DC, tophus, aggregates, erosion findings of 0.98, 0.71, 0.54 and 0.85, respectively. The mean intra-reader κ values were also acceptable: 0.93, 0.78, 0.65 and 0.78, respectively. Conclusion. This, the first consensus-based US definition of elementary lesions in gout, demonstrated good reliability overall. It constitutes an essential step in developing a core outcome measurement that permits a higher degree of homogeneity and comparability between multicentre studies

The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology

BACKGROUND: In 2001, the European League Against Rheumatism developed and disseminated the first guidelines for musculoskeletal (MS) ultrasound (US) in rheumatology. Fifteen years later, the dramatic expansion of new data on MSUS in the literature coupled with technological developments in US imaging has necessitated an update of these guidelines.OBJECTIVES: To update the existing MSUS guidelines in rheumatology as well as to extend their scope to other anatomic structures relevant for rheumatology.METHODS: The project consisted of the following steps: (1) a systematic literature review of MSUS evaluable structures; (2) a Delphi survey among rheumatologist and radiologist experts in MSUS to select MS and non-MS anatomic structures evaluable by US that are relevant to rheumatology, to select abnormalities evaluable by US and to prioritise these pathologies for rheumatology and (3) a nominal group technique to achieve consensus on the US scanning procedures and to produce an electronic illustrated manual (ie, App of these procedures).RESULTS: Structures from nine MS and non-MS areas (ie, shoulder, elbow, wrist and hand, hip, knee, ankle and foot, peripheral nerves, salivary glands and vessels) were selected for MSUS in rheumatic and musculoskeletal diseases (RMD) and their detailed scanning procedures (ie, patient position, probe placement, scanning method and bony/other landmarks) were used to produce the App. In addition, US evaluable abnormalities present in RMD for each anatomic structure and their relevance for rheumatology were agreed on by the MSUS experts.CONCLUSIONS: This task force has produced a consensus-based comprehensive and practical framework on standardised procedures for MSUS imaging in rheumatology

GRAPPA 2011: Proceedings from the ultrasound imaging module

In a plenary session at the 2011 meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) the use of sonography for evaluating enthesitis and dactylitis in psoriasis and psoriatic arthritis (PsA) was reviewed, and initial proposals were presented to develop ultrasound joint indices to assess enthesitis and dactylitis in PsA. Sonography can depict ultrastructural morphopathological features of an enthesis and its adjoining tissue structures, as well as increased vascularity; candidate entheses were proposed for an initial sonographic PsA enthesitis index. Ultrasound also can readily demonstrate soft tissue changes, synovitis, erosions, and osteoproliferation in dactylitis, and these features were proposed for an initial sonographic dactylitis index. A perspective was also presented on a wider proposed index including the skin, nail, joint, and enthesis. The Journal of Rheumatology Copyright \ua9 2012. All rights reserved

Ultrasound and magnetic resonance imaging in the evaluation of psoriatic dactylitis: Status and perspectives

Objective. Dactylitis, a characteristic feature of the spondyloarthropathies, occurs in up to 48% of patients with psoriatic arthritis (PsA). No clear consensus on the underlying components and pathogenesis of dactylitis exists in the literature. We undertook a systematic review of ultrasound (US) and magnetic resonance imaging (MRI) literature to better define imaging elements that contribute to the dactylitic digit seen in PsA. Our objectives were to determine first the level of homogeneity of each imaging modality's definition of the components of dactylitis, and second, to evaluate the metric properties of each imaging modality according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) filter. Methods. Searches were performed in PUBMED and EMBASE for articles pertaining to MRI, US, and dactylitis. Data regarding the reported features of dactylitis were collected and categorized, and the metrological qualities of the studies were assessed. Results. The most commonly described features of dactylitis were flexor tendon tenosynovitis and joint synovitis (90%). Extratendinous soft tissue thickening and extensor tendonitis were described nearly equally as being present and absent. Discrepancy exists as to whether entheses proper contribute to the etiology of dactylitis. An increasing number of studies categorize abnormalities in several tissue compartments including the soft tissue, tendon sheaths, and joints, as well as ligaments. Conclusion. The understanding of which tissues contribute to dactylitic inflammation has evolved. However, there is a lack of literature regarding the natural history of these abnormalities. This systematic review provides guidance in defining elementary lesions that may discriminate dactylitic digits from normal digits, leading to development of a composite measure of activity and severity of dactylitis. The Journal of Rheumatology Copyright \ua9 2013. All rights reserved

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

Management of dactylitis in patients with psoriatic arthritis: an updated literature review informing the 2021 GRAPPA treatment recommendations

Objective This literature review aimed to identify the most efficacious current interventions for dactylitis and provide up-to-date scientific evidence to support the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommendations on the management of psoriatic arthritis. Methods Original articles published from 2013 to 2020, registered in MEDLINE, Embase, and Cochrane Library, describing interventional trials and reporting dactylitis-related outcomes were included. The 20 members of the GRAPPA dactylitis group were divided into 9 subgroups according to treatment, and members of each group independently extracted data from articles/abstracts corresponding to their group by using a standardized data extraction form. Results Forty-nine publications were analyzed, representing 40 randomized clinical trials (RCTs) and including 16,752 patients. Dactylitis was assessed as a secondary outcome in 97.5% of these trials and more than 40% of RCTs did not employ a specific dactylitis measure or instrument. Conclusion The emergence of agents with novel mechanisms of action in recent years, such as interleukin 17 (IL-17), IL-12/23, IL-23, and Janus kinase inhibitors, has significantly expanded the available treatment options for dactylitis. This article points out the lack of consensus regarding dactylitis assessment and the paucity of data concerning the effect of local steroid injections, nonsteroidal antiinflammatory drugs, and conventional disease-modifying antirheumatic drugs. Clinical trials evaluating the effect of these traditional and low-cost medications used to treat dactylitis should be encouraged