Search

Objectives: To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV)., Methods: A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes., Results: Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation., Conclusions: The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV., Competing Interests: Competing interests: CDejaco has received consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos, Sparrow and Sanofi; grant support from AbbVie and Novartis, all unrelated to this manuscript. He is an editorial board member of ARD. SR has received research grants and/or consultancy fees From AbbVie, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sanofi, UCB. MB: consultancy fees from AbbVie PB has received speaker fees by Janssen and project grants by Pfizer. CP has received research grants and/or consultancy fees from AbbVie, Vifor, Roche, GlaxoSmithKline and AstraZeneca, all unrelated to this manuscript. SLM reports: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer and Novartis; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SLM is supported in part by the NIHR Leeds Biomedical Research Centre. TAB reports research grants from Deutsche Forschungsgemeinschaft (DFG) and Siemens Healthineers on behalf of his Department. He has received consulting/speaker’s fees from BioTel Research, Chugai, Guerbet, Novartis, Roche, Sanofi and Siemens Healthineers. DB consultancy fees from Roche and GSKSara Brolin: Grant from Novartis. MCC has received consulting fees from GSK, SCL-Vifor, AbbVie, AstraZeneca and Janssen, and a research grant form Kiniksa Pharmaceuticals. JM-C has received consulting/speaker’s fees from Abbvie, Lilly, Janssen, Novartis, Pfizer, UCB, MSD, all unrelated to this manuscript. BD has received consultancies and educational grants from Novartis, Abbvie, Roche, Chugai, Sanofi. BDN has received consulting/speaker’s fees from Roche and Novartis all unrelated to this manuscript. EDM Research funding/consulting and conferences fees from: Abbvie, Novartis, Pfizer, Roche, Janssen, Lilly, MSD, BMS, UCB, Grunental and Sanofi. CDuftner has received consulting/speaker’s fees from Abbvie, AOP Orphan, Astra-Zeneca, Bristol-Myers-Squibb, Eli-Lilly, Janssen, Galapagos, Merck-Sharp-Dohme, Novartis, Pfizer, Roche, Sandoz, UCB, Vifor, and grant/research support from Eli-Lilly, Pfizer, UCBHaner Direskeneli is investigator in clinical trials for Abbvie and Novartis, had educational support from Pfizer, Amgene, Celltrion, UCB and Roche unrelated to this manuscript. AM has received research grants and/or consultancy fees From AbbVie, BMS, Biogen, Eli Lilly, Galapagos, Janssen, MSD, Novartis and UCB. LS has received grant support from the Swiss Society of Rheumatology, iQone and Sandoz and support for travel expenses from Sanofi; all unrelated to this manuscript. RHJAS has received independent research grants of Siemens Healtineers and WAS has received consultancy fees, honoraria and travel expenses from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, and Sanofi and is principal investigator in trials sponsored by Abbvie, GlaxoSmithKline, Novartis and Sanofi., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)., Methods: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously., Results: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment., Conclusion: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research., Competing Interests: Competing interests: CDe has received consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Sparrow, Roche, Galapagos and Sanofi, all unrelated to this manuscript. He is an editorial board member of ARD. AK has received consultancy fees, honoraria and travel expenses from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, Janssen, Merck Sharp and Dohme, Novartis, UCB and Pfizer, all unrelated to this manuscript. He is an editorial board member of ARD. DA received grants, speaker fees, and/or consultancy fees from Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz and Sanofi. He is an editorial board member of ARD. MB has received consulting fees from AbbVie. DC has received speaker fees from Abiogen, BMS and GSK. MCC received consultancy and/or speaker fees from GSK, Vifor, Abbvie, Astra Zeneca and Janssen and a research grant form Kiniksa Pharmaceuticals. BD has received consultancies from Novartis, Abbvie, Roche and speaker agreements from Chugai. CDu has received consultancy or speaker fees and travel expenses from Abbvie, AOP Orphan, Astra-Zeneca, Bristol-Myers-Squibb, Eli-Lilly, Janssen, Galapagos, Merck-Sharp-Dohme, Novartis, Pfizer, Roche, Sandoz, UCB, Vifor and research support by Eli-Lilly, Pfizer, UCB, all unrelated to this manuscript. BH received speaker fees and/or consultancies from Abbvie, Amgen, Astra-Zeneca, BMS, Boehringer, Chugai, GSK, InflaRx, Janssen, MSD, Pfizer, Novartis, Phadia, Roche and Vifor. ELM has received consulting fees from Boehringer-Ingelheim, Horizon Therapeutics, Alvotech Inc; speaker fees from Boehringer-Ingelheim; royalties from UpToDate. SPM has received consultancy fees (Invex Therapeutics); advisory board fees (Invex therapeutics; Gensight) and speaker fees (Heidelberg engineering; Chugai-Roche Ltd; Allergan; Santen; Teva UK; Chiesi; and Santhera). All unrelated to this manuscript. LN has received consulting fees from AbbVie. CP is or has been the principal investigator of studies by AbbVie, Sanofi and Novartis and has received consulting/speaker’s fees from Vifor, AstraZeneca, GlaxoSmithKline and Roche, all unrelated to this manuscript. CS has received consultancy fees from Abbvie, Boehringer-Ingelheim, Eli Lilly, Galapagos, Novartis, Pfizer and Roche and royalties from UpToDate. All unrelated to this manuscript. SES has received research support by Astra-Zeneca and has done provided unpaid consultancy for Sanofi. SES is supported by the Rheumatology Research Foundation RISE pilot award and Bristol Myers Squibb Foundation Robert A Winn Diversity in Clinical Trials Career Development Award, outside of the submitted work. WAS has received consultancy fees, honoraria and travel expenses from Abbvie, Amgen, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, Johnson & Johnson, Medac, Novartis, Roche, and Sanofi and is principal investigator in trials sponsored by Abbvie, Amgen, GlaxoSmithKline, Novartis, Roche and Sanofi. PS has received consultancy fees from Amgen and Janssen and royalties from UpToDate, all unrelated to this manuscript. JSS received grants to his institution from Abbvie, AstraZeneca, Lilly, Novartis and Roche and provided expert advice for, or had symposia speaking engagements with, AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celltrion, Chugai, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, R-Pharm, Roche, Samsung, Sanofi and UCB. He is the editor in chief of ARD. JT has received consultancy or speaker fees Bristol-Myers-Squibb, Novartis, Glaxo-Smith-Kline, Astra-Zeneca, Janssen, Abbvie, Eli-Lilly. All unrelated to this manuscript. CET-G has received consultancy fees, honoraria and travel expenses from Abbvie, BMS, Boehringer Ingelheim, Biopas, Janssen, Pfizer, Pharmalab, Roche, all unrelated to this manuscript. FB has received consultancy fees, honoraria and travel expenses from Abbvie, Novartis, Pfizer, Roche and Sanofi, all unrelated to this manuscript. He is an editorial board member of ARD. EH, LE, AA, SA, PCG, AH, TAK and MW declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties., Methods: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24., Results: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corr coeff 0.37-0.48)., Conclusion: We developed a provisional OGUS for potential use in clinical trials., Competing Interests: Competing interests: CDe has received grant support from AbbVie and consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Galapagos, Novartis, Pfizer, Sparrow, Roche and Sanofi, all unrelated to this manuscript. CPo is or has been the principal investigator of studies by AbbVie, Sanofi and Novartis and has received consulting/speaker’s fees from Vifor, AstraZeneca, GlaxoSmithKline and Roche, all unrelated to this manuscript. LT received speakers fee from Roche, Novartis, Janssen, Pfizer, UCB and GE. PB received grant support from Pfizer and speaker’s fees from Janssen. CDu has received consultancy or speaker fees and travel expenses from Abbvie, AOP Orphan, Astra-Zeneca, Bristol-Myers-Squibb, Eli-Lilly, Janssen, Galapagos, Merck-Sharp-Dohme, Novartis, Pfizer, Roche, Sandoz, UCB, Vifor and research support from Eli-Lilly, Pfizer, UCB, all unrelated to this manuscript. E-MH has received fees for speaking and/or consulting from Novartis, AbbVie, Sanofi, Sobi; research funding to Aarhus University Hospital from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis, AbbVie; travel expenses from Pfizer, Sobi, AbbVie. E-MH has been the principal investigator of studies by SynACT Pharma and involved as site principal investigator in trials by AbbVie, Novartis, Novo and Sanofi, all unrelated to this manuscript. AI received honoraria, advisory boards, speakers’ bureau, educational grants and research support from AbbVie, Alfasigma, Amgen, Biogen, BMS, Celgene, Celltrion, Eli-Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, Sanofi Genzyme, SOBI and UCB. KDT is or was a research investigator of studies for Novartis, Astra Zeneca, Glaxo SmithKline, Amgen; has received consulting fees from Aurinia, Novartis and Astra Zeneca; and is a contracted researcher of Bioclinica. KSMvdG received a speaker fee from Roche. WAS is or has been the principal investigator of studies by Abbvie, Amgen, GlaxoSmithKline, Novartis, Roche, Sanofi and has received consulting/speaker’s fees from Abbvie, Amgen, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, Johnson & Johnson, Medac, Novartis, Roche and Sanofi, all unrelated to this manuscript. The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Remote care and telehealth have the potential to expand healthcare access, and the COVID-19 pandemic has called for alternative solutions to conventional face-to-face follow-up and monitoring. However, guidance is needed on the integration of telehealth into clinical care of people with rheumatic and musculoskeletal diseases (RMD)., Objective: To develop EULAR points to consider (PtC) for the development, prioritisation and implementation of telehealth for people with RMD., Methods: A multidisciplinary EULAR task force (TF) of 30 members from 14 European countries was established, and the EULAR standardised operating procedures for development of PtC were followed. A systematic literature review was conducted to support the TF in formulating the PtC. The level of agreement among the TF was established by anonymous online voting., Results: Four overarching principles and nine PtC were formulated. The use of telehealth should be tailored to patient's needs and preferences. The healthcare team should have adequate equipment and training and have telecommunication skills. Telehealth can be used in screening for RMD as preassessment in the referral process, for disease monitoring and regulation of medication dosages and in some non-pharmacological interventions. People with RMD should be offered training in using telehealth, and barriers should be resolved whenever possible.The level of agreement to each statement ranged from 8.5 to 9.8/10., Conclusion: The PtC have identified areas where telehealth could improve quality of care and increase healthcare access. Knowing about drivers and barriers of telehealth is a prerequisite to successfully establish remote care approaches in rheumatologic clinical practice., Competing Interests: Competing interests: AN has received consulting and/or speaker’s fees from UCB, CHUGAI, BMS all unrelated to this manuscript. YM has received speakers fees from Pfizer unrelated to this manuscript. AdT has received an unrestricted grant from Novartis, and speakers fee from Pfizer and Eli Lily unrelated to this manuscript. CD has received consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos and Sanofi, all unrelated to this manuscript., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To develop evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs)., Methods: European Alliance of Associations for Rheumatology (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound (US), fluoroscopy, MRI, CT and fusion imaging to guide interventional procedures. Based on evidence and expert opinion, the task force (25 participants consisting of physicians, healthcare professionals and patients from 11 countries) developed PtC, with consensus obtained through voting. The final level of agreement was provided anonymously., Results: A total of three overarching principles and six specific PtC were formulated. The task force recommends preference of imaging over palpation to guide targeted interventional procedures at peripheral joints, periarticular musculoskeletal structures, nerves and the spine. While US is the favoured imaging technique for peripheral joints and nerves, the choice of the imaging method for the spine and sacroiliac joints has to be individualised according to the target, procedure, expertise, availability and radiation exposure. All imaging guided interventions should be performed by a trained specialist using appropriate operational procedures, settings and assistance by technical personnel., Conclusion: These are the first EULAR PtC to provide guidance on the role of imaging to guide interventional procedures in patients with RMDs., Competing Interests: Competing interests: CDejaco has received consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos and Sanofi, all unrelated to this manuscript. PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, and is supported by the National Institute for Health Research (NIHR), University College London Hospitals (UCLH), Biomedical Research Centre (BRC). FC has received consulting/speaker’s fees from Abbvie and Celgene, all unrelated to this manuscript. LT has received speakers fee from Novartis, UCB, Roche and Pfizer. GT has received research grants from Iqone and received consulting/speaker’s fees from Menarini, all unrelated to this manuscript. LMS has received consulting/speaker’s fees from Janssen-Cilag, Novartis, Pfizer, Abiogen, Samsung Medison, Esaote, all unrelated to this manuscript. FP has received research grants from Novartis and UCB and received consulting/speaker’s fees from Abbvie, AMGEN, BMS, Hexal, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this manuscript. CP has received honoraria and/or research and development grants from: Abbott/AbbVie, Astellas, Astra-Zeneca/MedImmune, BMS, CelGene, Grunenthal, GSK, Janssen/J&J, MSD, Pfizer, Sanofi, Roche/Genentech/Chugai, UCB. HBH has received fees for speaking and/or consulting from AbbVie, BMS, Pfizer, UCB, Roche, MSD and Novartis. WH has received fees for speaking and/or consulting from AbbVie, Alpinion, Canon, Celgene, Chugai, Janssen-Cilag, Pfizer, Roche. CDuftner has received consulting/speaker’s fees from Abbvie, BMS, Eli Lilly, Janssen, Novartis, Pfizer, Roche and UCB, all unrelated to this manuscript. PVB has received consulting/speaker’s fees from Abbvie, BMS, Celgene,Celltrion, Eli Lilly, IBSA, Janssen-Cilag, MSD, Novartis, Pfizer, Professional Publishing Hungary, Richter, Roche, Sandoz, Springer Nature, UCB, all unrelated to this manuscript. XB has received consulting/speaker’s fees or grant support from Abbvie, Amgen, BMS, Chugai, Galapagos, Gilead, Hexal, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, all unrelated to this manuscript., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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 [ 18 F]-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., Competing Interests: Competing interests: TAB received research grants from Deutsche Forschungsgemeinschaft (DFG) and Siemens Healthineers and received consultancies and speaker fees from HeartFlow, GSK, MSD, Roche, Bayer, Bracco, Guerbet and Siemens. EB received consultancies and speaker fees from Roche, which were paid to the University Medical Center Groningen. BD has received consultancies from Roche, GSK and Munidipharma. APD received speaker fees from Roche. WS received consultancies and speakers fee from Roche and GSK. All other authors have no competing interest., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To investigate the possible occurrence of early thymic failure and premature senescence of naïve and memory T-cells in patients with axial spondyloarthritis (aSpA)., Methods: Prospective, cross-sectional study of consecutive patients with aSpA (n=51), rheumatoid arthritis (RA, n=51) and healthy controls (HCs, n=50). Demographic, clinical and laboratory parameters were collected in all patients and we isolated naïve (CD45RA(+)) and memory (CD45RO(+)) CD4(+) and CD8(+) T-cell subsets by MACS technology. T-cell receptor rearrangement excision circle (TREC) and telomere length were measured by real-time PCR. We used TRECs as a surrogate for thymus function and telomere length as an indicator of cellular senescence. Telomerase activity was analysed with the Telomeric Repeat Amplification Protocols., Results: We observed a premature decline of thymic output in patients with aSpA and patients with RA compared with HCs as indicated by a reduction of TREC levels in naive T-cells (aSpA: age adjusted regression coefficient (regcoeff) for CD4(+)CD45RA(+) T-cells -2.566, p=0.023; RA regcoeff=-2.844, p=0.008). Telomere length of all CD4(+) and CD8(+) T-cell subsets was reduced in young patients with aSpA compared with HCs, whereas data for patients with RA were comparable with HCs. Telomerase activity was inversely correlated with telomere length in HCs (correlation coefficient (corcoeff)=-0.532, p<0.001) but not in patients with aSpA (corcoeff=-0.056, p=0.697) and RA (corcoeff=-0.003, p=0.982)., Conclusions: Our data indicate an age-inappropriate shrinkage of thymic output, an inappropriate shortening of telomeres in young patients with aSpA and an impaired telomerase enzyme in patients with aSpA and RA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To investigate the association between psoriatic arthritis (PsA)-specific clinical composite scores and ultrasound-verified pathology as well as comparison of clinical and ultrasound definitions of remission., Methods: We performed a prospective study on 70 consecutive PsA patients. Clinical assessments included components of Disease Activity Index for Psoriatic Arthritis (DAPSA) and the Composite Psoriatic Disease Activity Index (CPDAI). Minimal disease activity (MDA) and the following remission criteria were applied: CPDAI joint, entheses and dactylitis domains (CPDAI-JED)=0, DAPSA≤3.3, Boolean's remission definition and physician-judged remission (rem-phys). B-mode and power Doppler (PD-) ultrasound findings were semiquantitatively scored at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses. Ultrasound remission and minimal ultrasound disease activity (MUDA) were defined as PD-score=0 and PD-score ≤1, respectively, at joints, peritendinous tissue, tendons and entheses., Results: DAPSA but not CPDAI correlated with B-mode and PD-synovitis. Ultrasound signs of enthesitis, dactylitis, tenosynovitis and perisynovitis were not linked with clinical composites. Clinical remission or MDA was observed in 15.7% to 47.1% of PsA patients. Ultrasound remission and MUDA were present in 4.3% and 20.0% of patients, respectively. Joint and tendon-related PD-scores were higher in patients with active versus inactive disease according to CPDAI-JED, DAPSA, Boolean's and rem-phys, whereas no difference was observed regarding enthesitis and perisynovitis. DAPSA≤3.3 (OR 3.9, p=0.049) and Boolean's definition (OR 4.6, p=0.03) were more useful to predict MUDA than other remission criteria., Conclusions: PsA-specific composite scores partially reflect ultrasound findings. DAPSA and Boolean's remission definitions better identify MUDA patients than other clinical criteria., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To investigate functional expression of NKG2D on CD4 and CD8 T-cells in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)., Methods: Peripheral blood was drawn from patients with GCA (n=16), PMR (n=78) and healthy controls (HC, n=64). Tissue samples were obtained from GCA patients and controls. Proliferation and cytokine production assays were performed using CFSE and intracellular IFN-γ or TNF-α staining, respectively, and flow cytometry analysis. Immunofluorescence and immunohistology were applied to analyse the presence of NKG2D-expressing T-cells and NKG2D-ligands in temporal arteries, respectively. mRNA levels of NKG2D-ligands were determined by RT-PCR., Results: In both GCA and PMR patients, NKG2D was preferentially expressed on senescent CD4CD28(-) and CD8CD28(-), as well as on CD8CD28 T-cells. Frequencies of senescent T-cells were increased in GCA and PMR patients compared to HC. In GCA tissue samples, infiltrating T-cells were predominately CD28(-). NKG2D expressing T-cells concentrated around the vasa vasorum of the adventitia. Antigenic stimulation induced rapid up-regulation of NKG2D on CD4CD28(-) and CD4CD28 T-cells, whereas TNF-α and interleukin-15 enhanced NKG2D expression on senescent CD4 and CD8 T-cells only. NKG2D cross-linkage augmented anti-CD3 triggered proliferation, IFN-γ and TNF-α production of CD8 T-cells. In CD4CD28(-) T-cells, NKG2D ligation resulted in increased IFN-γ production only. NKG2D ligands were expressed in temporal arteries from GCA patients, particularly in the adventitial and medial layers of affected vessels., Conclusions: NKG2D is functionally expressed on CD4CD28(-) and CD8 T-cells in GCA and PMR. NKG2D-ligands are present in temporal arteries and may co-stimulate NKG2D expressing T-cells.

The objective of this study was to develop EULAR/ACR 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 RF and/or ACPA (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 CRP and/or ESR and new hip pain. These criteria are not meant for diagnostic purposes.

Objective: To compare current definitions of remission and relapse in polymyalgia rheumatica (PMR) with items resulting from a Delphi-based expert consensus., Methods: Relevant studies including definitions of PMR remission and relapse were identified by literature search in PubMed. The questionnaire used for the Delphi survey included clinical (n=33), laboratory (n=54) and imaging (n=7) parameters retrieved from a literature search. Each item was assessed for importance and availability/practicability, and limits were considered for metric parameters. Consensus was defined by an agreement rate of ≥80%., Results: Out of 6031 articles screened, definitions of PMR remission and relapse were available in 18 and 34 studies, respectively. Parameters used to define remission and/or relapse included history and clinical assessment of pain and synovitis, constitutional symptoms, morning stiffness (MS), physician's global assessment, headache, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count, fibrinogen and/or corticosteroid therapy. In the Delphi exercise a consensus was obtained on the following parameters deemed essential for definitions of remission and relapse: patient's pain assessment, MS, ESR, CRP, shoulder and hip pain on clinical examination, limitation of upper limb elevation, and assessment of corticosteroid dose required to control symptoms., Conclusions: Assessment of patient's pain, MS, ESR, CRP, shoulder pain/limitation on clinical examination and corticosteroid dose are considered to be important in current available definitions of PMR remission and relapse and the present expert consensus. The high relevance of clinical assessment of hips was unique to this study and may improve specificity and sensitivity of definitions for remission and relapse in PMR.

Objectives: To study the clinical outcome, treatment response, T-cell subsets and functional consequences of a novel tumour necrosis factor (TNF) receptor type 1 (TNFRSF1A) mutation affecting the receptor cleavage site., Methods: Patients with symptoms suggestive of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and 22 healthy controls (HC) were screened for mutations in the TNFRSF1A gene. Soluble TNFRSF1A and inflammatory cytokines were measured by ELISAs. TNFRSF1A shedding was examined by stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol 12-myristate 13-acetate followed by flow cytometric analysis (FACS). Apoptosis of PBMCs was studied by stimulation with TNFalpha in the presence of cycloheximide and annexin V staining. T cell phenotypes were monitored by FACS., Results: TNFRSF1A sequencing disclosed a novel V173D/p.Val202Asp substitution encoded by exon 6 in one family, the c.194-14G>A splice variant in another and the R92Q/p.Arg121Gln substitution in two families. Cardiovascular complications (lethal heart attack and peripheral arterial thrombosis) developed in two V173D patients. Subsequent etanercept treatment of the V173D carriers was highly effective over an 18-month follow-up period. Serum TNFRSF1A levels did not differ between TRAPS patients and HC, while TNFRSF1A cleavage from monocytes was significantly reduced in V173D and R92Q patients. TNFalpha-induced apoptosis of PBMCs and T-cell senescence were comparable between V173D patients and HC., Conclusions: The TNFRSF1A V173D cleavage site mutation may be associated with an increased risk for cardiovascular complications and shows a strong response to etanercept. T-cell senescence does not seem to have a pathogenetic role in affected patients.