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To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Background: Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells-the target for rituximab-in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status.Methods: This study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28.Findings: Between Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI -11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [-1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [-5 to 10]) were not significantly different between treatment groups.Interpretation: The results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice.Funding: Efficacy and Mechanism Evaluation programme from the UK National Institute for Health Research. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) represents the most common form of primary systemic vasculitis and is frequently associated with comorbidities related to the disease itself or induced by the treatment. Systematically collected data on disease course, treatment and outcomes of GCA remain scarce. The aim of this EULAR Task Force was to identify a core set of items which can easily be collected by experienced clinicians, in order to facilitate collaborative research into the course and outcomes of GCA. A multidisciplinary EULAR task force group of 20 experts including rheumatologists, internists, epidemiologists and patient representatives was assembled. During a 1-day meeting, breakout groups discussed items from a previously compiled collection of parameters describing GCA status and disease course. Feedback from breakout groups was further discussed. Final consensus was achieved by means of several rounds of email discussions after the meeting. A three-round Delphi survey was conducted to determine a core set of parameters including the level of agreement. 117 parameters were regarded as relevant. Potential items were subdivided into the following categories: General, demographics, GCA-related signs and symptoms, other medical conditions and treatment. Possible instruments and assessment intervals were proposed for documentation of each item. To facilitate implementation of the recommendations in clinical care and clinical research, a minimum core set of 50 parameters was agreed. This proposed core set intends to ensure that relevant items from different GCA registries and databases can be compared for the dual purposes of facilitating clinical research and improving clinical care., Competing Interests: Competing interests: JA has or has had research agreements with Abbvie, BMS, MSD, Pfizer, Roche, Astra-Zeneca, Eli Lilly, Samsung Bioepis and UCB, mainly in the context of safety monitoring of biologics via ARTIS. Karolinska Institutet has received remuneration for JA participating in advisory boards arranged by Pfizer and Eli Lilly. HWJB reported serving as coordinating investigator (Roche and SUN) in GCA and GC trials and consultant and speaker for Roche. MCC reported receiving consultation/lecturing fees from Roche, GSK, Novartis, Boehringer-Ingelheim, Vifor and Abbvie and research funding from Kiniksa. MC reported serving as coordinating investigator (Mundipharma, Horizon) and consultant (Mundipharma, Horizon) in PMR trials. BD reported clinical trials design advisory board consultancies (Roche, Servier, GSK, Mundipharma, Pfizer, Merck, Sobi) and unrestricted grant support from Napp and Roche and speakers honoraria from UCB and Merck. CD reported receiving consultancy fees and honoraria from MSD, Pfizer, UCB, AbbVie, Roche, Novartis, Lilly, Celgene, Merck, Sandoz, clinical trials design advisory board consultancies from GSK and an unrestricted grant support from Pfizer and MSD. WGD reported that the University of Manchester has received remuneration for WGD providing consultancy to Bayer. NF is an employee of the Swedish Medical Products Agency (MPA). AF received speaker honoraria or consultancies within the past 5 years from AbbVie, AB2BIO, BMS, Eli-Lilly, MSD, Pfizer, Roche, not related to the submitted work. KG has received consultancy fees from PMRGCAuk re facilitation of patient engagement with medical research in PMR and GCA. SLM has been an investigator for GCA trials (Roche, GSK), has had medical advisory group consultancies (Roche, Sanofi, Chugai) and is a Patron of the charities PMRGCAuk and PMR and GCA North East. AM reported receiving consultancy fees and honoraria from Roche-Chugai. EM reported serving as coordinating investigator (Novartis) and consultant (Glaxo-Smith-Kline) in PMR trials, consultant (Glaxo-Smith-Kline, Endocyte) and as site investigator in GCA trials (Bristol Meyer Squibb, Hoffman-La Roche, Genentech, Glaxo-Smith-Kline) and editor, contributor for PMR/GCA (UpToDate, Paradigm). CS reported serving as coordinating investigator (Roche) and consultant (Roche) in GCA trials. WAS reported receiving consultancy fees, honoraria and a grant support from Roche, consultancy fees and honoraria from GlaxoSmithKline and consultancy fees from Sanofi. He was principle investigator in a GCA trial (GlaxoSmithKline). AS received speaker honoraria within the past 5 years from AbbVie, BMS, Lilly, MSD, Pfizer, Roche, Sanofi-Aventis and UCB outside the submitted work. RFvV reported receiving research support and grants from AbbVie, BMS, GSK, Pfizer and UCB. He served as consultant for AbbVie, AstraZeneca, Biotest, BMS, Celgene, Crescendo, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Roche and UCB. FB reported receiving consultancy fees, honoraria and travel expenses from Horizon Pharma (formerly Nitec Pharma), Mundipharma Int. Ltd, Roche and Galapagos and grant support from Horizon Pharma. He serves as co-principal investigator and site investigator in a Mundipharma sponsored trial in PMR investigating the effects of MR prednisone., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10 -54 , per-allele OR = 1.79; and rs9275592, p = 1.14 × 10 -40 , OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10 -10 , OR = 1.28; and rs128738, p = 4.60 × 10 -9 , OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR., (© 2015, American College of Rheumatology.)

Objective: This report summarizes the findings from a consensus process to identify potential classification criteria for polymyalgia rheumatica (PMR)., Methods: A 3-stage hybrid consensus approach was used to develop potential PMR classification criteria. The first stage consisted of a facilitated meeting of 27 international experts who anonymously rated the importance of 68 potential criteria. The second stage involved a meeting of the experts, who were provided with the results of the first round of ratings and were then asked to re-rate the criteria. In the third stage, the wider acceptance of the 43 criteria that received > 50% support at round 2 was evaluated using an extended mailed survey of 111 rheumatologists and 53 nonrheumatologists in the United States, Canada, and Northern and Western Europe., Results: A total of 68 and 50 criteria were identified and rated in round 1 and round 2, respectively. In round 2, 43 of the 50 items achieved at least 50% support, including 10 core criteria achieving 100% support. In round 3, over 70% of survey respondents agreed on the importance of 7 core criteria. These were age >or=50 years, duration >or=2 weeks, bilateral shoulder and/or pelvic girdle aching, duration of morning stiffness > 45 min, elevated erythrocyte sedimentation rate, elevated C-reactive protein, and rapid steroid response (> 75% global response within 1 wk to prednisolone/prednisone 15 20 mg daily). Among physical signs, more than 70% of survey respondents agreed on the importance of assessing pain and limitation of shoulder (84%) and/or hip (76%) on motion, but agreement was low for peripheral signs like carpal tunnel, tenosynovitis, and peripheral arthritis., Conclusion: There are differences in opinion as to what PMR is and how it should be treated. These findings make it important to develop classification criteria for PMR. The next step is to perform an international prospective study to evaluate the utility of candidate classification criteria for PMR in patients presenting with the polymyalgic syndrome.