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Objectives: Ageing and inflammation are associated with clonal haematopoiesis (CH), the emergence of somatic mutations in haematopoietic cells. This study details CH in patients with systemic vasculitis in association with clinical, haematological and immunological parameters., Methods: Patients with three forms of vasculitis were screened for CH in peripheral blood by error-corrected sequencing. Relative contributions of age and vasculitis on CH prevalence were calculated using multivariable logistic regression. Clonal hierarchies were assessed by proteogenomic single-cell DNA sequencing, and functional experiments were performed in association with CH status., Results: Patients with Takayasu's arteritis (TAK; n=70; mean age=33.2 years), antineutrophil cytoplasmic antibody-associated vasculitis (AAV; n=47; mean age=55.3 years) and giant cell arteritis (GCA; n=59; mean age=71.2 years) were studied. CH, most commonly in DNMT3A and TET2, was detected in 34% (60/176) of patients versus 18% (28/151) of age-matched controls (p<0.01). Prevalence of CH was independently associated with age (standardised B=0.96, p<0.01) and vasculitis (standardised B=0.46, p<0.01), occurring in 61%, 32% and 13% of patients with GCA, AAV and TAK, respectively. Both branched and linear clonal trajectories showed myeloid-lineage bias, and CH was associated with markers of cellular activation. In GCA, mutations were detected in temporal artery biopsies, and clinical relapse correlated with CH in a dose-dependent relationship with clone size., Conclusions: Age was more strongly associated with CH prevalence than inflammation in systemic vasculitis. Clonal profile was dominated by DNMT3A mutations which were associated with relapse in GCA. CH is not likely a primary causal factor in systemic vasculitis but may contribute to inflammation., Competing Interests: Competing interests: None declared., (© 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.)

Markers of extracellular mitochondria are present in giant cell arteritis (GCA) patients. However, their role in promoting inflammation and platelet activation is no known. To investigate this, isolated mitochondria were opsonized with plasma from GCA patients or healthy individuals and incubated with peripheral blood mononuclear cells (PBMCs) or platelets and assessed for inflammatory cytokine production and platelet activation. Plasma from GCA patients promoted increased mitochondrial-mediated cytokine production by PBMCs as compared to healthy controls (p < 0.05). Mitochondria opsonized with plasma factors from patients with GCA induced higher platelet activation as compared to mitochondria opsonized with plasma factors from healthy individuals (p = 0.0015). Platelet levels of P-selectin were associated with disease activity in GCA (r = 0.34, p = 0.01). GCA patients have impaired ability to regulate the clearance of extracellular mitochondria, possibly contributing to excessive inflammation and platelet activation. Targeting key drivers of mitochondrial extrusion and/or their clearance could lead to new therapeutic interventions in GCA., Competing Interests: Declaration of Competing Interest Dr. Michailidou received Advisory Board fees from ChemoCentryx. Dr. Khalidi received clinical trial support from BMS, Sanofi and Abbvie, travel support from Astra Zeneca, and Advisory Board fee from Roche. Dr. Koening served on the advisory board for Chemocentryx and Genentech. Dr. Sreih works at Bristol-Myers Squibb and owns Astra Zeneca and Alexion stock. Dr. Warrington received clinical trial support from Eli Lilly, BMS and Kiniksa, and consulting fees from Chemocentryx. Dr. Monach received consulting fees from Kiniksa, Celgene/BMC, and ChemoCentryx. Dr. Merkel reports receiving funds for the following activities: Consulting and Research Support: AbbVie, Amgen, AstraZeneca, Boeringher-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, InflaRx, Takeda. Consulting only: ArGenx, Cabaletta, CSL Behring, HiBio, Janssen, Jubilant, Kyverna, MiroBio, Novartis, NS Pharma, Q32, Regeneron, Sparrow, Vistera. Research Support only: Eicos, Electra, Forbius, Genentech/Roche, Genzyme/Sanofi, Neutrolis. Stock options: Kyverna. Royalties: UpToDate. Dr. Lood received research funding from Pfizer, Gilead Sciences, Boehringer Ingelheim, Redd Pharma, Amytryx, and Eli Lilly., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine and compare disease activity over time in giant cell arteritis (GCA) and Takayasu arteritis (TAK) using multimodal assessment combining clinical, laboratory, and imaging-based testing., Methods: Patients with GCA or TAK were enrolled into a single-center prospective, observational cohort at any point in the disease course. Patients underwent standardized assessment, including 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) at enrollment and follow-up visits. Each FDG-PET finding was subjectively interpreted as active or inactive vasculitis. Global arterial FDG uptake was quantified by the PET Vascular Activity Score (PETVAS). Patients were stratified by disease duration at enrollment (0-2 years; 2-5 years; >5 years). Fisher exact and Mann-Whitney U tests, Spearman's correlation, and linear regression were used for statistical analyses., Results: A total of 126 patients with large vessel vasculitis (GCA = 50; TAK = 76) were evaluated across 319 visits. Clinical disease activity was present in 33% of patients in the second to fifth year of disease and in 24% of patients evaluated >5 years after diagnosis. Active vasculitis by PET was observed in 66% of patients in years 2 to 5 after diagnosis and in 50% of patients enrolled >5 years into disease. PETVASs were consistently higher in GCA than TAK in the early and later phases of disease and significantly decreased over time in GCA but not TAK. Correlations between clinical, laboratory, and imaging findings were complex and varied with disease duration., Conclusion: Disease activity in GCA and TAK is common throughout the disease course. Patterns of vascular PET activity at diagnosis and later in disease differ between GCA and TAK., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: To evaluate the feasibility of tocilizumab tapering and withdrawal in patients with giant cell arteritis (GCA)., Methods: GCA patients eligible for tocilizumab were prospectively enrolled. Tocilizumab was administered weekly for the first 12 months, every-other-week for an additional 12 months, then discontinued. Relapses on tocilizumab were managed with temporary increases in systemic glucocorticoids or addition of methotrexate. Primary outcome was relapse-free survival at month 6 after tocilizumab suspension. Relapse-free survival on tocilizumab, imaging response, and adverse events were evaluated., Results: 23 GCA patients were enrolled. Reasons for tocilizumab start were relapse (n = 14), persistence of activity (n = 5), or steroid-related adverse events (n = 4). At tocilizumab start, two patients were on methotrexate, which was maintained. Fourteen patients had extracranial vascular involvement on 18 FDG-PET/CT. During the first 12 months, four patients (17%) had clinical relapse. At every-other-week tocilizumab start, all patients were in clinical remission, two patients had active vasculitis on 18 FDG-PET/CT; two patients were on steroid therapy, and four patients were taking methotrexate. Two patients (9%) relapsed while on every-other-week tocilizumab. At tocilizumab suspension, no patient was on steroid therapy and no patient had signs of active vasculitis on 18 FDG-PET/CT. In the 6 months after tocilizumab discontinuation, six patients (26%) relapsed. No new or unexpected safety findings were identified., Conclusion: Tocilizumab tapered over a two-year period was effective to induce and maintain remission in GCA. Relapses on tocilizumab were minor and responded to incremental changes in therapy. A significant proportion of patients relapsed in the 6 months after therapy suspension., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Levels of neutrophil extracellular traps (NETs) were measured in plasma of healthy controls (HC, n = 30) and patients with granulomatosis with polyangiitis (GPA, n = 123), microscopic polyangiitis (MPA, n = 61), Takayasu's arteritis (TAK, n = 58), and giant cell arteritis (GCA, n = 68), at times of remission or activity and correlated with levels of the platelet-derived thrombospondin-1 (TSP-1). Levels of NETs were elevated during active disease in patients with GPA (p < 0.0001), MPA (p = 0.0038), TAK (p < 0.0001), and GCA (p < 0.0001), and in remission for GPA, p < 0.0001, MPA, p = 0.005, TAK, p = 0.03, and GCA, p = 0.0009. All cohorts demonstrated impaired NET degradation. Patients with GPA (p = 0.0045) and MPA (p = 0.005) had anti-NET IgG antibodies. Patients with TAK had anti-histone antibodies (p < 0.01), correlating with presence of NETs. Levels of TSP-1 were increased in all patients with vasculitis, and associated with NET formation. NET formation is a common process in vasculitides. Targeting NET formation or degradation could be potential therapeutic approaches for vasculitides., Competing Interests: Declaration of Competing Interest Dr. Michailidou received Advisory Board fees from ChemoCentryx. Dr. Khalidi received clinical trial support from BMS, Sanofi and Abbvie, travel support from Astra Zeneca, and Advisory Board fee from Roche. Dr. Koening served on the advisory board for Chemocentryx and Genentech. Dr. Specks reports receiving funds for the following activities: Consulting: AstraZeneca, ChemoCentryx. Research Support: AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Genentech/Roche, InflaRx. Dr. Sreih works at Bristol-Myers Squibb and owns Astra Zeneca and Alexion Stocks. Dr. Warrington received clinical trial support from Eli Lilly and Kiniksa. Dr. Monach received consulting fees from Kiniksa, Celgene/BMC, and ChemoCentryx. Dr. Merkel reports receiving funds for the following activities: Consulting and Research Support: AbbVie, AstraZeneca, Boeringher-Ingelheim, Bristol-Myers Squibb, ChemoCentryx, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Takeda. Consulting only: CSL Behring, Dynacure, EMDSerono, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, Pfizer, Sparrow, Talaris. Royalties: UpToDate. Dr. Lood received research funding from Pfizer, Gilead Sciences, Boehringer Ingelheim, Redd Pharma, Amytryx, and Eli Lilly., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The use of fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging to detect vascular inflammation is increasingly common in the clinical management of patients with large-vessel vasculitis (LVV). In this review, the role of FDG-PET imaging to diagnose and monitor vascular disease activity will be detailed. Suggestions on incorporation of FDG-PET imaging into a clinical workflow will be provided with emphasis on patient preparation, image acquisition, and image interpretation. If FDG-PET imaging is obtained, multimodal imaging assessment, whereby FDG-PET imaging and non-invasive angiography are obtained concurrently, and correlation of imaging findings with clinical assessment is generally advisable. Considering the clinical scenario and treatment status of the patient is important when interpreting vascular FDG-PET image findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Objective: To assess whether vascular activity seen on 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan is associated with angiographic change in large vessel vasculitis (LVV)., Methods: Patients with LVV were recruited into a prospective cohort. All patients underwent magnetic resonance angiography or computed tomography angiography and FDG-PET imaging. Follow-up imaging using the same imaging modalities was obtained ≥6 months later per a standardized imaging protocol. Arterial damage, defined as stenosis, occlusion, or aneurysm, and corresponding FDG uptake were evaluated in 17 arterial territories. On follow-up, development of new lesions was recorded, and existing lesions were characterized as improved, worsened, or unchanged., Results: A total of 1,091 arterial territories from 70 patients with LVV (38 patients with Takayasu arteritis, 32 patients with giant cell arteritis) were evaluated. Over a median 1.6 years of follow-up, new lesions developed only in 8 arterial territories in 5 patients with Takayasu arteritis. Arterial lesions improved in 16 territories and worsened in 6 territories. Most arterial territories that did not have vascular activity on FDG-PET scan at baseline had no angiographic change over the follow-up period (787 [99%] of 793). Few territories with baseline FDG-PET activity had angiographic change over time (24 [8%] of 298), but of the territories that developed angiographic change, 80% had FDG-PET activity at baseline. Within the same patient, an arterial territory with baseline FDG-PET activity had significantly increased risk for angiographic change compared to a paired arterial territory without FDG-PET activity (odds ratio 19.49 [95% confidence interval 2.44-156.02]; P < 0.01). Concomitant edema and wall thickening further increased risk for angiographic change., Conclusion: Development of angiographic change was infrequent in this cohort of patients with LVV. A lack of baseline FDG-PET activity was strongly associated with stable angiographic disease. In cases of angiographic progression, change was preceded by the presence of FDG-PET activity., (© 2022 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: To develop and validate updated classification criteria for giant cell arteritis (GCA)., Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate items, (2) prospective collection of candidate items present at the time of diagnosis, (3) expert panel review of cases, (4) data-driven reduction of candidate items, (5) derivation of a points-based risk classification score in a development data set and (6) validation in an independent data set., Results: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C reactive protein ≥10 mg/L (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging and fluorodeoxyglucose-positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% CI 0.88 to 0.94) with a sensitivity of 87.0% (95% CI 82.0% to 91.0%) and specificity of 94.8% (95% CI 91.0% to 97.4%)., Conclusion: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess markers of neutrophil activation such as calprotectin and N-formyl methionine (fMET) in anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) and large-vessel vasculitis (LVV)., Methods: Levels of fMET, and calprotectin, were measured in the plasma of healthy controls (n=30) and patients with AAV (granulomatosis with polyangiitis (GPA, n=123), microscopic polyangiitis (MPA, n=61)), and LVV (Takayasu's arteritis (TAK, n=58), giant cell arteritis (GCA, n=68)), at times of remission or flare. Disease activity was assessed by physician global assessment. In vitro neutrophil activation assays were performed in the presence or absence of formyl peptide receptor 1 (FPR1) inhibitor cyclosporine H., Results: Levels of calprotectin, and fMET were elevated in patients with vasculitis as compared to healthy individuals. Levels of fMET correlated with markers of systemic inflammation: C-reactive protein (r=0.82, p<0.0001), and erythrocyte sedimentation rate (r=0.235, p<0.0001). The neutrophil activation marker, calprotectin was not associated with disease activity. Circulating levels of fMET were associated with neutrophil activation (p<0.01) and were able to induce de novo neutrophil activation via FPR1-mediated signaling., Conclusion: Circulating fMET appears to propagate neutrophil activation in AAV and LVV. Inhibition of fMET-mediated FPR1 signaling could be a novel therapeutic intervention for systemic vasculitides., (© 2022. The Author(s).)

Objective: In addition to aiding in diagnosis, histopathologic findings from temporal artery biopsy (TAB) specimens in giant cell arteritis (GCA) may be valuable for their associations with clinical features of the disease. This study was undertaken to compare histopathologic findings on TAB with biopsy interpretation and demographic, clinical, and imaging features at time of diagnosis., Methods: Patients with a clinical diagnosis of GCA who had a TAB were selected from an international, multicenter observational cohort of vasculitis. Associations between demographic, clinical, radiographic, and histopathologic features were identified using bivariate testing and multivariate regression modeling., Results: Of 705 patients with GCA who underwent TAB, 69% had histopathologic evidence of definite vasculitis. Specific histopathologic findings included the presence of giant cells (51%), fragmentation of the internal elastic lamina (41%), intimal thickening (33%), and predominantly mononuclear leukocyte infiltration (32%). Histopathologic interpretation of definite vasculitis was independently associated with giant cells (odds ratio [OR] 151.8 [95% confidence interval (95% CI) 60.2-551.6]), predominantly mononuclear leukocyte infiltration (OR 11.8 [95% CI 5.9-24.9]), and fragmentation of the internal elastic lamina (OR 3.7 [95% CI 1.9-7.4]). A halo sign on temporal artery ultrasound and luminal damage of large arteries on angiography were significantly associated with presence of giant cells (OR 2.6 [95% CI 1.1-6.5] and OR 2.4 [95% CI 1.1-5.2], respectively). Specific histopathologic findings were associated with older age, but no associations were identified with vision loss or other clinical features., Conclusion: Histopathologic findings in GCA are strongly associated with the clinical diagnosis of GCA but have a limited role in identifying patterns of disease., (© 2020 American College of Rheumatology.)

The study rationale was to assess the performance of qualitative and semiquantitative scoring methods for 18 F-FDG PET assessment in large-vessel vasculitis. Methods: Patients with giant cell arteritis or Takayasu arteritis underwent independent clinical and imaging assessments within a prospective observational cohort. 18 F-FDG PET/CT scans were interpreted for active vasculitis by central reader assessment. Arterial 18 F-FDG uptake was scored by qualitative visual assessment using the PET vascular activity score (PETVAS) and by semiquantitative assessment using SUVs and target-to-background ratios (TBRs) relative to liver or blood activity. The performance of each scoring method was assessed by intrarater reliability using the intraclass correlation coefficient (ICC) and areas under the receiver-operating-characteristic curve, applying physician assessment of clinical disease activity and reader interpretation of vascular PET activity as independent reference standards. The Wilcoxon signed-rank test was used to analyze change in arterial 18 F-FDG uptake over time. Results: Ninety-five patients (giant cell arteritis, 52; Takayasu arteritis, 43) contributed 212 18 F-FDG PET studies. The ICC for semiquantitative evaluation (0.99 [range, 0.98-1.00]) was greater than the ICC for qualitative evaluation (0.82 [range, 0.56-0.93]). PETVAS and target-to-background ratio metrics were more strongly associated with reader interpretation of PET activity than SUV metrics. All assessment methods were significantly associated with physician assessment of clinical disease activity, but the semiquantitative metric liver tissue-to-background ratio (TBR Liver ) achieved the highest area under the receiver-operating-characteristic curve (0.66). Significant but weak correlations with C-reactive protein were observed for SUV metrics ( r = 0.19, P < 0.01) and TBR Liver ( r = 0.20, P < 0.01) but not for PETVAS. In response to increased treatment in 56 patients, arterial 18 F-FDG uptake was significantly reduced when measured by semiquantitative (TBR Liver , 1.31-1.23; 6.1% change; P < 0.0001) or qualitative (PETVAS, 22-18; P < 0.0001) methods. Semiquantitative metrics provided information complementary to qualitative evaluation in cases of severe vascular inflammation. Conclusion: Both qualitative and semiquantitative methods of measuring arterial 18 F-FDG uptake are useful in assessing and monitoring vascular inflammation in large-vessel vasculitis. Compared with qualitative metrics, semiquantitative methods have superior reliability and better discriminate treatment response in cases of severe inflammation., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Large-vessel vasculitis (LVV) manifests as inflammation of the aorta and its major branches and is the most common primary vasculitis in adults. LVV comprises two distinct conditions, giant cell arteritis and Takayasu arteritis, although the phenotypic spectrum of primary LVV is complex. Non-specific symptoms often predominate and so patients with LVV present to a range of health-care providers and settings. Rapid diagnosis, specialist referral and early treatment are key to good patient outcomes. Unfortunately, disease relapse remains common and chronic vascular complications are a source of considerable morbidity. Although accurate monitoring of disease activity is challenging, progress in vascular imaging techniques and the measurement of laboratory biomarkers may facilitate better matching of treatment intensity with disease activity. Further, advances in our understanding of disease pathophysiology have paved the way for novel biologic treatments that target important mediators of disease in both giant cell arteritis and Takayasu arteritis. This work has highlighted the substantial heterogeneity present within LVV and the importance of an individualized therapeutic approach. Future work will focus on understanding the mechanisms of persisting vascular inflammation, which will inform the development of increasingly sophisticated imaging technologies. Together, these will enable better disease prognostication, limit treatment-associated adverse effects, and facilitate targeted development and use of novel therapies., (© 2022. Springer Nature Limited.)

Objectives: To evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in GCA., Methods: Patients with GCA treated with tocilizumab were selected from a prospective, observational cohort. Patients underwent FDG-PET at the baseline visit prior to initiation of tocilizumab and at subsequent follow-up visits performed at 6-month intervals. All imaging findings were interpreted blinded to clinical data. The PET vascular activity score (PETVAS) was used to quantify arterial FDG uptake. Wilcoxon signed rank test was used to compare change in PETVAS between visits. Linear regression was used to determine change in PETVAS over multiple timepoints., Results: Twenty-five patients with GCA were included. All patients had physician-determined active vasculitis at the baseline visit by clinical assessment and FDG-PET interpretation. PETVAS was significantly reduced in association with tocilizumab treatment from the baseline to the most recent follow-up visit [24.0 (IQR 22.3-27.0) vs 18.5 (IQR 15.3-23.8); P <0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (P <0.01 for linear trend), with a similar degree of improvement in both the first and second years of treatment. Repeat FDG-PET scans after tocilizumab discontinuation showed worsening PET activity in five out of six patients, with two patients subsequently experiencing clinical relapse., Conclusion: Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure., (Published by Oxford University Press on behalf of the British Society for Rheumatology 2021. This work is written by US Government employees and is in the public domain in the US.)

Objective: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis., Methods: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel., Results: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions., Conclusion: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions., (© 2021 American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Objective: To assess the validity and clinical utility of the Brief Illness Perception Questionnaire (BIPQ) to measure illness perceptions in multiple forms of vasculitis., Methods: Patients with giant cell arteritis (GCA), Takayasu arteritis (TA), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), and relapsing polychondritis (RP) were recruited into a prospective, observational cohort. Patients independently completed the BIPQ, Multidimensional Fatigue Inventory (MFI), Medical Outcomes Study 36-item Short Form survey (SF-36), and a patient global assessment (PtGA) at successive study visits. Physicians concurrently completed a physician global assessment (PGA) form. Illness perceptions, as assessed by the BIPQ, were compared to responses from the full-length Revised Illness Perception Questionnaire (IPQ-R) and to other clinical outcome measures., Results: There were 196 patients (GCA = 47, TA = 47, RP = 56, AAV = 46) evaluated over 454 visits. Illness perception scores in each domain were comparable between the BIPQ and IPQ-R (3.28 vs 3.47, P = 0.22). Illness perceptions differed by type of vasculitis, with the highest perceived psychological burden of disease in RP. The BIPQ was significantly associated with all other patient-reported outcome measures (rho = |0.50-0.70|, P < 0.0001), but did not correlate with PGA (rho = 0.13, P = 0.13). A change in the BIPQ composite score of ≥ 7 over successive visits was associated with concomitant change in the PtGA. Change in the MFI and BIPQ scores significantly correlated over time (rho = 0.38, P = 0.0008)., Conclusion: The BIPQ is an accurate and valid assessment tool to measure and monitor illness perceptions in patients with vasculitis. Use of the BIPQ as an outcome measure in clinical trials may provide complementary information to physician-based assessments.

Objective: To identify and validate, using computer-driven methods, patterns of arterial disease in Takayasu arteritis (TAK) and giant cell arteritis (GCA)., Methods: Patients with TAK or GCA were studied from the Diagnostic and Classification Criteria for Vasculitis (DCVAS) cohort and a combined North American cohort. Case inclusion required evidence of large-vessel involvement, defined as stenosis, occlusion, or aneurysm by angiography/ultrasonography, or increased 18 F-fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) in at least 1 of 11 specified arterial territories. K-means cluster analysis identified groups of patients based on the pattern of arterial involvement. Cluster groups were identified in the DCVAS cohort and independently validated in the North American cohort., Results: A total of 1,068 patients were included (DCVAS cohort: TAK = 461, GCA = 217; North American cohort: TAK = 225, GCA = 165). Six distinct clusters of patients were identified in DCVAS and validated in the North American cohort. Patients with TAK were more likely to have disease in the abdominal vasculature, bilateral disease of the subclavian and carotid arteries, or focal disease limited to the left subclavian artery than GCA (P < 0.01). Patients with GCA were more likely to have diffuse disease, involvement of bilateral axillary/subclavian arteries, or minimal disease without a definable pattern than TAK (P < 0.01). Patients with TAK were more likely to have damage by angiography, and patients with GCA were more likely to have arterial FDG uptake by PET without associated vascular damage., Conclusion: Arterial patterns of disease highlight both shared and divergent vascular patterns between TAK and GCA and should be incorporated into classification criteria for large-vessel vasculitis., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: To assess the relationship between measures of disease assessment in patients with large vessel vasculitis., Methods: Patients with giant cell arteritis (GCA) or Takayasu arteritis (TAK) were recruited into a prospective, observational cohort. Assessments within the following outcomes were independently recorded: 1) patient-reported outcomes (Multidimensional Fatigue Inventory, patient global assessment of disease activity [PtGA], Short Form 36 health survey [SF-36], Brief Illness Perception Questionnaire), 2) physician global assessment of disease activity (PhGA), 3) laboratory outcomes (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR]), and 4) imaging outcomes (PETVAS, a qualitative score of vascular 18 F-fluorodeoxyglucose-positron emission tomography activity)., Results: Analyses were performed on 112 patients (GCA = 56, TAK = 56), over 296 visits, with a median follow-up of 6 months. Correlation network analysis revealed assessment measures clustered independently by type of outcome. PhGA was centrally linked to all other outcome types, but correlations were modest (ρ = 0.12-0.32; P < 0.05). PETVAS, CRP level, and PtGA were independently associated with clinically active disease. All 4 patient-reported outcomes strongly correlated with each other (ρ = 0.35-0.60; P < 0.0001). Patient-reported outcomes were not correlated with PETVAS, and only PtGA correlated with CRP level (ρ = 0.16; P < 0.01). Patients whose clinical assessment changed from active disease to remission (n = 29) had a corresponding significant decrease in ESR, CRP level, and PETVAS at the remission visit. Patients whose clinical assessment changed from remission to active disease (n = 11) had a corresponding significant increase in CRP level and PtGA at the active visit., Conclusion: Measures of disease assessment in large vessel vasculitis consist of independent, yet complementary, outcomes, supporting the need to develop composite outcome measures or a standard set of measures covering multiple types of outcomes., (© 2019, American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Objective: Diagnostic assessment in giant cell arteritis (GCA) is rapidly changing as vascular imaging becomes more available. This study was undertaken to determine if clinical GCA subsets have distinct profiles or reflect differential diagnostic assessments., Methods: Patients were recruited from an international cohort and divided into 4 subsets based on a temporal artery (TA) abnormality (positive TA biopsy [TAB] or halo sign on TA ultrasound [TA-US]) and/or evidence of large vessel (LV) involvement on imaging: 1) both TA abnormality and LV involvement (TA+/LV+ GCA); 2) TA abnormality without LV involvement (TA+/LV- GCA); 3) LV involvement without TA abnormality (TA-/LV+ GCA); and 4) clinically diagnosed GCA without LV involvement or TA abnormality (TA-/LV- GCA)., Results: Nine hundred forty-one patients with GCA were recruited from 72 international study sites. Most patients received multiple forms of diagnostic assessment, including TAB (n = 705 [75%]), TA-US (n = 328 [35%]), and LV imaging (n = 534 [57%]). Assessment using TAB, TA-US, and LV imaging confirmed the diagnosis of GCA in 66%, 79%, and 40% of cases, respectively. GCA subsets had distinct profiles independent of diagnostic assessment strategies. TA+/LV- were the most common subset (51%), with a high burden of cranial ischemia. Those in the TA-/LV- subset (26%) had a high prevalence of cranial ischemia and musculoskeletal symptoms. Patients in the TA-/LV+ subset (12%) had prevalent upper extremity vascular abnormalities and a low prevalence of vision loss, and those in the TA+/LV+ subset (11%) were older and had a high prevalence of cranial ischemia, constitutional symptoms, and elevated acute-phase reactant levels., Conclusion: Vascular imaging is increasingly incorporated into the diagnostic assessment of GCA and identifies clinical subsets of patients based on involvement of temporal and extracranial arteries., (© 2019, American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Objective: To compare the presence of head, neck and upper extremity symptoms in patients with Takayasu's (TAK) and giant cell arteritis (GCA) and their association with vascular inflammation assessed by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) or arterial damage assessed by magnetic resonance angiography (MRA)., Methods: Patients with TAK and GCA underwent clinical and imaging assessments within 24 hours, blinded to each other. Vascular inflammation was defined as arterial FDG-PET uptake greater than liver by visual assessment. Arterial damage was defined as stenosis, occlusion, or aneurysm by MRA. Clinically reported symptoms were compared with corresponding imaging findings using generalised mixed model regression. Cranial symptoms were studied in association with burden of arterial disease in the neck using ordinal regression., Results: Participants with TAK (n=56) and GCA (n=54) contributed data from 270 visits. Carotidynia was reported only in patients with TAK (21%) and was associated with vascular inflammation (p<0.01) but not damage (p=0.33) in the corresponding carotid artery. Posterior headache was reported in TAK (16%) and GCA (20%) but was only associated with corresponding vertebral artery inflammation and damage in GCA (p<0.01). Arm claudication was associated with subclavian artery damage (p<0.01) and inflammation (p=0.04) in TAK and with damage in GCA (p<0.01). Patients with an increased burden of damaged neck arteries were more likely to experience positional lightheadedness (p<0.01) or a major central nervous system event (p=0.01)., Conclusion: The distribution of symptoms and association with imaging abnormalities differs in patients with TAK and GCA. These findings may help clinicians predict associated FDG-PET and MRA findings based on a specific clinical symptom., Clinical Trial Registration Number: NCT02257866., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine the impact of imaging acquisition time on interpretation of disease activity on 18 F-fluorodeoxyglucose positron emission tomography (PET) in large-vessel vasculitis (LVV) and assess the relationship between clinical features and image acquisition time., Methods: Patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK) were recruited into a prospective, observational cohort. After a single injection of FDG, all patients underwent two sequential PET scans at one and two-hour time points. Images were interpreted for active vasculitis by subjective assessment, qualitative assessment, and semi-quantitative assessment. Agreement was assessed by percent agreement, Cohen's kappa, and McNemar's test. Multivariable logistic regression identified associations between PET activity and clinical variables., Results: 79 patients (GCA  =  44, TAK  =  35) contributed 168 paired one and two-hour PET studies. A total of 94 out of 168 scans (56%) were interpreted as active at the one-hour time point, and 129 scans (77%) were interpreted as active at the two-hour time point (p < 0.01). Associations between clinical variables and PET activity categories (dual inactive, delayed active, dual active) were evaluated. Using multivariable nominal regression, clinically active disease was significantly more common in patients in the delayed active group (Odds Ratio 1.94, 95%CI 1.13-3.53; p  =  0.02) and the dual active group (Odds Ratio 1.71, 95%CI 1.06-2.93; p  =  0.04) compared to the dual inactive group., Conclusions: Imaging protocol significantly influences interpretation of PET activity in LVV. A substantial proportion of patients with LVV have PET activity only detected by delayed imaging. These patients were significantly more likely to have concomitant clinically-determined active disease., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Published by Elsevier Inc.)

Objective: Disease activity in large-vessel vasculitis (LVV) is traditionally assessed by clinical and serological variables rather than vascular imaging. This study determined the effect of treatment on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) vascular activity in relation to clinical- and serologic-based assessments., Methods: Patients with giant cell arteritis (GCA) or Takayasu arteritis (TA) were prospectively evaluated at 6-month intervals in an observational cohort. Treatment changes were made at least 3 months before the followup visit and categorized as increased, decreased, or unchanged. Imaging (FDG-PET qualitative analysis), clinical, and serologic (erythrocyte sedimentation rate, C-reactive protein) assessments were determined at each visit and compared over interval visits., Results: Serial assessments were performed in 52 patients with LVV (GCA = 31; TA = 21) over 156 visits. Increased, decreased, or unchanged therapy was recorded for 36-, 23-, and 32-visit intervals, respectively. When treatment was increased, there was significant reduction in disease activity by imaging, clinical, and inflammatory markers (p ≤ 0.01 for each). When treatment was unchanged, all 3 assessments of disease activity remained similarly unchanged over 6-month intervals. When treatment was reduced, PET activity significantly worsened (p = 0.02) but clinical and serologic activity did not significantly change. Treatment of GCA with tocilizumab and of TA with tumor necrosis factor inhibitors resulted in significant improvement in imaging and clinical assessments of disease activity, but only rarely did the assessments both become normal., Conclusion: In addition to clinical and serologic assessments, vascular imaging has potential to monitor disease activity in LVV and should be tested as an outcome measure in randomized clinical trials.

Objective: Calcification of the coronary arteries, aorta, and branch vessels can occur in both large-vessel vasculitis (LVV) and atherosclerosis. The study objective was to determine the location and amount of vascular calcification in patients with LVV versus hyperlipidemia (HLD) and to identify risk factors associated with vascular calcification in LVV., Methods: Patients with giant cell arteritis (GCA), Takayasu's arteritis (TAK), and HLD underwent non-contrast computed tomography of the aorta and branch vessels. Vascular calcification in 14 specific arterial territories (4 segments of the aorta, 9 branch arteries, and the coronary arteries) was quantified throughout the large arteries by a cumulative Agatston score. Multivariate linear regression analyses were used to identify associations between traditional and disease-specific risk factors and total Agatston score., Results: A total of 88 subjects, including GCA (n = 29); TAK (n = 22); and HLD (n = 37), participated. Prevalence of vascular calcification in the aorta and branch vessels significantly differed in the coronary arteries (HLD = 67%, GCA = 35%, TAK = 9%, p < 0.01). Total Agatston scores were higher in GCA (median 3260, range 25-18,138) versus HLD (460, 19-17,215) (p < 0.01) but did not significantly differ between GCA and TAK (1944, 52-47,520) (p = 0.53). In multivariable regression analysis, age, type of vasculitis, and prednisone use was associated with vascular calcification in LVV., Conclusion: The prevalence of coronary artery calcification is lower in LVV compared to HLD, but the amount of total vascular calcification throughout the large arteries is greater in LVV. Both traditional and disease-specific risk factors are associated with vascular calcification in LVV., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To assess agreement between interpretation of magnetic resonance angiography (MRA) and 18 F-fluorodeoxyglucose positron emission tomography (PET) for disease extent and disease activity in large-vessel vasculitis (LVV) and determine associations between imaging and clinical assessments., Methods: Patients with giant cell arteritis (GCA), Takayasu's arteritis (TAK) and comparators were recruited into a prospective, observational cohort. Imaging and clinical assessments were performed concurrently, blinded to each other. Agreement was assessed by per cent agreement, Cohen's kappa and McNemar's test. Multivariable logistic regression identified MRA features associated with PET scan activity., Results: Eighty-four patients (GCA=35; TAK=30; comparator=19) contributed 133 paired studies. Agreement for disease extent between MRA and PET was 580 out of 966 (60%) arterial territories with Cohen's kappa=0.22. Of 386 territories with disagreement, MRA demonstrated disease in more territories than PET (304vs82, p<0.01). Agreement for disease activity between MRA and PET was 90 studies (68%) with Cohen's kappa=0.30. In studies with disagreement, MRA demonstrated activity in 23 studies and PET in 20 studies (p=0.76). Oedema and wall thickness on MRA were independently associated with PET scan activity. Clinical status was associated with disease activity by PET (p<0.01) but not MRA (p=0.70), yet 35/69 (51%) patients with LVV in clinical remission had active disease by both MRA and PET., Conclusions: In assessment of LVV, MRA and PET contribute unique and complementary information. MRA better captures disease extent, and PET scan is better suited to assess vascular activity. Clinical and imaging-based assessments often do not correlate over the disease course in LVV., Trial Registration Number: NCT02257866., Competing Interests: Competing interests: None declared., (© 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 assess the clinical value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large vessel vasculitis (LVV) and comparator subjects., Methods: Patients with Takayasu arteritis and giant cell arteritis were studied, along with a comparator group consisting of patients with hyperlipidemia, patients with diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG-PET imaging, and patients with LVV underwent serial imaging at 6-month intervals. We calculated sensitivity and specificity of FDG-PET interpretation for distinguishing patients with clinically active LVV from comparator subjects and from patients with disease in clinical remission. A qualitative summary score based on global arterial FDG uptake, the PET Vascular Activity Score (PETVAS), was used to study associations between activity on PET scan and clinical characteristics and to predict relapse., Results: A total of 170 FDG-PET scans were performed in 115 participants (56 patients with LVV and 59 comparator subjects). FDG-PET distinguished patients with clinically active LVV from comparator subjects with a sensitivity of 85% (95% confidence interval [95% CI] 69, 94) and a specificity of 83% (95% CI 71, 91). FDG-PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71 [58%]). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with activity on PET scan. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high PETVAS than in those with a low PETVAS (55% versus 11%; P = 0.03) over a median follow-up period of 15 months., Conclusion: FDG-PET provides information about vascular inflammation that is complementary to, and distinct from, clinical assessment in LVV. FDG-PET scan activity during clinical remission was associated with future clinical relapse., (© 2017, American College of Rheumatology.)

Objectives: Alterations in the immune system and infections are suspected to increase susceptibility to giant cell arteritis (GCA). Recently herpes zoster has been directly implicated in the pathogenesis of GCA. We examined the association between prior infections, in particular herpes zoster, and incident GCA in a population-based cohort., Methods: A nested case-control study was performed using an electronic database from the UK. Cases with newly diagnosed GCA were identified using a validated algorithm and compared with age-matched, sex-matched and practice-matched controls. Conditional logistic regression was used to examine the relationship between any infection or herpes zoster infection on the development of GCA after adjusting for potential confounders; results were expressed as incidence rate ratios (IRRs)., Results: There were 4559 cases of GCA and 22 795 controls. Any prior infection and herpes zoster were associated with incident GCA (IRR 1.26 (95% CI 1.16 to 1.36), p<0.01; and 1.17 (95% CI 1.04 to 1.32), p<0.01, respectively). A greater number of infections was associated with a higher risk of developing GCA (IRR for 1, 2-4 and ≥5 infections was 1.28, 1.60 and 2.18, respectively)., Conclusions: Antecedent infections and, to a lesser extent, herpes zoster infections are modestly associated with incident GCA. These data provide population-level support for the hypothesis that long-standing alterations of the immune system are associated with susceptibility to GCA and suggest that herpes zoster is unlikely to play a major causal role in the pathogenesis of GCA., Competing Interests: Competing interests: Intercontinental Marketing Services (IMS) Health Real World Evidence Solutions is an UK-based expert in anonymous patient data for the healthcare industry. IMS Health is a commercial organisation that supplies data and trains and supports researchers in the use of primary care patient data. Data are available for us in medical research in the academic setting as well as in industry for a fee which varies depending on the type of data requested. Aside from undergoing ethical review by The Health Improvement Network (THIN) Scientific Review Committee, independent academic groups who voluntarily act as an ethical review body, this protocol was not in any way discussed with IMS Health nor were any changes made by the company. We did not receive financial support or other forms of computational or analytical support from IMS/THIN. The data were collected by IMS and the general practitioners without knowledge of the study objectives and hypotheses., (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/.)

Objectives: To compare patterns of arteriographic lesions of the aorta and primary branches in patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA)., Methods: Patients were selected from two North American cohorts of TAK and GCA. The frequency of arteriographic lesions was calculated for 15 large arteries. Cluster analysis was used to derive patterns of arterial disease in TAK versus GCA and in patients categorised by age at disease onset. Using latent class analysis, computer derived classification models based upon patterns of arterial disease were compared with traditional classification., Results: Arteriographic lesions were identified in 145 patients with TAK and 62 patients with GCA. Cluster analysis demonstrated that arterial involvement was contiguous in the aorta and usually symmetric in paired branch vessels for TAK and GCA. There was significantly more left carotid (p=0.03) and mesenteric (p=0.02) artery disease in TAK and more left and right axillary (p<0.01) artery disease in GCA. Subclavian disease clustered asymmetrically in TAK and in patients ≤55 years at disease onset and clustered symmetrically in GCA and patients >55 years at disease onset. Computer derived classification models distinguished TAK from GCA in two subgroups, defining 26% and 18% of the study sample; however, 56% of patients were classified into a subgroup that did not strongly differentiate between TAK and GCA., Conclusions: Strong similarities and subtle differences in the distribution of arterial disease were observed between TAK and GCA. These findings suggest that TAK and GCA may exist on a spectrum within the same disease.

Objective: To assess the utility of the vascular physical examination to detect arteriographic lesions in patients with established large vessel vasculitis (LVV), including Takayasu's arteritis (TAK) and giant cell arteritis (GCA)., Methods: In total, 100 patients (TAK = 68, GCA = 32) underwent standardized physical examination and angiography of the carotid, subclavian, and axillary arteries. Sensitivity and specificity were calculated for the association between findings on physical examination focusing on the vascular system (absent pulse, bruit, and blood pressure difference) and arteriographic lesions defined as stenosis, occlusion, or aneurysm., Results: We found 67% of patients had at least 1 abnormality on physical examination (74% TAK, 53% GCA). Arteriographic lesions were seen in 76% of patients (82% TAK, 63% GCA). Individual physical examination findings had poor sensitivity (range 14%-50%) and good-excellent specificity (range 71%-98%) to detect arteriographic lesions. Even when considering physical examination findings in combination, at least 30% of arteriographic lesions were missed. Specificity improved (range 88%-100%) if individual physical examination findings were compared to a broader region of vessels rather than specific anatomically correlated vessels and if ≥ 1 physical examination findings were combined., Conclusion: In patients with established LVV, physical examination alone is worthwhile to detect arterial disease but does not always localize or reveal the full extent of arteriographic lesions. Abnormal vascular system findings on physical examination are highly associated with the presence of arterial lesions, but normal findings on physical examination do not exclude the possibility of arterial disease. Serial angiographic assessment is advisable to monitor arterial disease in patients with established LVV.

Objective: To assess whether vascular activity seen on 18F‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) scan is associated with angiographic change in large vessel vasculitis (LVV). Methods: Patients with LVV were recruited into a prospective cohort. All patients underwent magnetic resonance angiography or computed tomography angiography and FDG‐PET imaging. Follow‐up imaging using the same imaging modalities was obtained ≥6 months later per a standardized imaging protocol. Arterial damage, defined as stenosis, occlusion, or aneurysm, and corresponding FDG uptake were evaluated in 17 arterial territories. On follow‐up, development of new lesions was recorded, and existing lesions were characterized as improved, worsened, or unchanged. Results: A total of 1,091 arterial territories from 70 patients with LVV (38 patients with Takayasu arteritis, 32 patients with giant cell arteritis) were evaluated. Over a median 1.6 years of follow‐up, new lesions developed only in 8 arterial territories in 5 patients with Takayasu arteritis. Arterial lesions improved in 16 territories and worsened in 6 territories. Most arterial territories that did not have vascular activity on FDG‐PET scan at baseline had no angiographic change over the follow‐up period (787 [99%] of 793). Few territories with baseline FDG‐PET activity had angiographic change over time (24 [8%] of 298), but of the territories that developed angiographic change, 80% had FDG‐PET activity at baseline. Within the same patient, an arterial territory with baseline FDG‐PET activity had significantly increased risk for angiographic change compared to a paired arterial territory without FDG‐PET activity (odds ratio 19.49 [95% confidence interval 2.44–156.02]; P < 0.01). Concomitant edema and wall thickening further increased risk for angiographic change. Conclusion: Development of angiographic change was infrequent in this cohort of patients with LVV. A lack of baseline FDG‐PET activity was strongly associated with stable angiographic disease. In cases of angiographic progression, change was preceded by the presence of FDG‐PET activity. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate updated classification criteria for giant cell arteritis (GCA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate items, 2) prospective collection of candidate items present at the time of diagnosis, 3) expert panel review of cases, 4) data‐driven reduction of candidate items, 5) derivation of a points‐based risk classification score in a development data set, and 6) validation in an independent data set. Results: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C‐reactive protein ≥10 mg/liter (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging, and fluorodeoxyglucose–positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% confidence interval [95% CI] 0.88–0.94) with a sensitivity of 87.0% (95% CI 82.0–91.0%) and specificity of 94.8% (95% CI 91.0–97.4%). Conclusion: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research. [ABSTRACT FROM AUTHOR]

Noncerebral vasculitis is a wide-range noninfectious inflammatory disorder affecting the vessels. Vasculitides have been categorized based on the vessel size, such as large-vessel vasculitis, medium-vessel vasculitis, and small-vessel vasculitis. In this document, we cover large-vessel vasculitis and medium-vessel vasculitis. Due to the challenges of vessel biopsy, imaging plays a crucial role in diagnosing this entity. While CTA and MRA can both provide anatomical details of the vessel wall, including wall thickness and enhancement in large-vessel vasculitis, FDG-PET/CT can show functional assessment based on the glycolytic activity of inflammatory cells in the inflamed vessels. Given the size of the vessel in medium-vessel vasculitis, invasive arteriography is still a choice for imaging. However, high-resolution CTA images can depict small-caliber aneurysms, and thus can be utilized in the diagnosis of medium-vessel vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in GCA. Methods Patients with GCA treated with tocilizumab were selected from a prospective, observational cohort. Patients underwent FDG-PET at the baseline visit prior to initiation of tocilizumab and at subsequent follow-up visits performed at 6-month intervals. All imaging findings were interpreted blinded to clinical data. The PET vascular activity score (PETVAS) was used to quantify arterial FDG uptake. Wilcoxon signed rank test was used to compare change in PETVAS between visits. Linear regression was used to determine change in PETVAS over multiple timepoints. Results Twenty-five patients with GCA were included. All patients had physician-determined active vasculitis at the baseline visit by clinical assessment and FDG-PET interpretation. PETVAS was significantly reduced in association with tocilizumab treatment from the baseline to the most recent follow-up visit [24.0 (IQR 22.3–27.0) vs 18.5 (IQR 15.3–23.8); P  <0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (P  <0.01 for linear trend), with a similar degree of improvement in both the first and second years of treatment. Repeat FDG-PET scans after tocilizumab discontinuation showed worsening PET activity in five out of six patients, with two patients subsequently experiencing clinical relapse. Conclusion Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure. [ABSTRACT FROM AUTHOR]

Objective: To provide evidence‐based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. Methods: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. Results: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid‐sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. Conclusion: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions. [ABSTRACT FROM AUTHOR]

Objective: Pseudostenosis is a magnetic resonance angiography (MRA) artifact that mimics arterial stenosis. The study objective was to compare imaging and clinical aspects of stenosis and pseudostenosis in a cohort of large‐vessel vasculitis (LVV), including giant‐cell arteritis (GCA) and Takayasu's arteritis (TAK). Methods: Patients with LVV and comparator conditions (healthy or vasculopathies) underwent MRA of the aortic arch vessels. The subclavian and axillary arteries were systematically assessed for presence of stenosis and pseudostenosis by two independent readers. Serial and delayed imaging and clinical assessments were used to confirm suspected pseudostenoses. Multivariable regression analyses were used to identify associations between angiographic pathology and clinical findings. Results: One hundred eighty‐four MRA scans were analyzed from patients with GCA (n = 36), TAK (n = 47), and comparators (n = 25). Pseudostenoses were frequently observed (48 of 184 scans, 26%) in the distal subclavian artery only on the side of injection and were shorter in length compared with true stenoses (25 mm vs 78 mm, P < 0.01). There was no difference in prevalence of pseudostenosis by diagnosis (GCA = 33%, TAK = 23%, comparator = 20%, P = 0.44), disease activity status (P = 0.31), or treatment status (P = 1.00). Percent and length of true stenosis were independently associated with pulse and blood pressure abnormalities in the upper extremity. Adjusting for length and stenosis degree, absence of collateral arteries was associated with arm claudication (odds ratio = 2.37, P = 0.03). Conclusion: Although a pseudostenosis could be falsely interpreted as an arterial stenosis, radiographic and associated clinical features can help distinguish true disease from arterial susceptibility artifacts. In addition, the peripheral vascular examination can help to confirm a suspected true stenosis, as specific aspects of angiographic pathology are associated with vascular examination abnormalities in LVV. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical value of 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large vessel vasculitis (LVV) and comparator subjects. Methods: Patients with Takayasu arteritis and giant cell arteritis were studied, along with a comparator group consisting of patients with hyperlipidemia, patients with diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG‐PET imaging, and patients with LVV underwent serial imaging at 6‐month intervals. We calculated sensitivity and specificity of FDG‐PET interpretation for distinguishing patients with clinically active LVV from comparator subjects and from patients with disease in clinical remission. A qualitative summary score based on global arterial FDG uptake, the PET Vascular Activity Score (PETVAS), was used to study associations between activity on PET scan and clinical characteristics and to predict relapse. Results: A total of 170 FDG‐PET scans were performed in 115 participants (56 patients with LVV and 59 comparator subjects). FDG‐PET distinguished patients with clinically active LVV from comparator subjects with a sensitivity of 85% (95% confidence interval [95% CI] 69, 94) and a specificity of 83% (95% CI 71, 91). FDG‐PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71 [58%]). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with activity on PET scan. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high PETVAS than in those with a low PETVAS (55% versus 11%; P = 0.03) over a median follow‐up period of 15 months. Conclusion: FDG‐PET provides information about vascular inflammation that is complementary to, and distinct from, clinical assessment in LVV. FDG‐PET scan activity during clinical remission was associated with future clinical relapse. [ABSTRACT FROM AUTHOR]

Objectives. Advances in diagnostic techniques have led to better distinction between types of vasculitis, potentially affecting the utility of the 1990 ACR classification criteria for vasculitis. This study tested the performance of these criteria in a contemporary vasculitis cohort. Methods. The Diagnosis and Classification in Vasculitis Study provided detailed clinical, serological, pathological and radiological data from patients with primary systemic vasculitis and clinical context- specific comparator conditions. Fulfilment of six ACR criteria sets and their diagnostic performance was evaluated in patients with a given type of vasculitis and its comparator conditions. Results. Data from 1095 patients with primary systemic vasculitis and 415 with comparator conditions were available. For classification, sensitivities and specificities for ACR classification criteria were, respectively, 81.1% and 94.9% for GCA; 73.6% and 98.3% for Takayasu's arteritis; 65.6% and 88.7% for granulomatosis with polyangiitis; 57.0% and 99.8% for eosinophilic granulomatosis with polyangiitis; 40.6% and 87.8% for polyarteritis nodosa; 28.9% and 88.5% for microscopic polyangiitis; and 72.7% and 96.3% for IgA-vasculitis. Overall sensitivity was 67.1%. Of cases identified by their respective criteria, 16.9% also met criteria for other vasculitides. Diagnostic specificity ranged from 64.2 to 98.9%; overall, 113/415 comparators (27.2%) fulfilled at least one of the ACR classification criteria sets. Conclusion. Since publication of the ACR criteria for vasculitis, the sensitivity for each type of vasculitis, except GCA, has diminished, although the specificities have remained high, highlighting the need for updated classification criteria. [ABSTRACT FROM AUTHOR]