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Background: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations., Methods: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations., Results: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons., Conclusions: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice., Competing Interests: Competing interests: EB received consultancies from Roche (payed to the University Medical Center Groningen). FB received grants from Horizon and Mundipharma and speaker fees and/or consultancies from Horizon, Mundipharma, Roche and Sanofi. HB received a grant and speaker fees from Roche. BD received consultancies and/or speaker fees from BMS, Chugai, GSK and Roche. CD received and grant from Celgene and speaker fees and/or consultancies from Abbvie, BMS, Lilly, MSD, Pfizer, Novartis, UCB, Roche and Sanofi. BH received speaker fees and/or consultancies from Abbvie, Boehringer, Chugai, Celgene, MSD, Pfizer, Novartis and Roche. SM received speaker fees and consultancies from Roche and Chugai. WS received a grant from Roche and speaker fees and consultancies from Chugai, GSG, Novartis, Roche and Sanofi. CT received a grant from BMS and speaker fees and/or consultancies from Abbvie, BMS, Pfizer and Roche. PV received a grant for conducting an RCT in GCA from Roche. All other authors have no competing interests., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares., Methods: Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week prednisone taper (PBO + Pred-26), or placebo plus 52-week prednisone taper (PBO + Pred-52). Outcome measures were prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare., Results: One hundred patients received TCZ-QW + Pred-26, 49 received TCZ-Q2W + Pred-26, 50 received PBO + Pred-26, and 51 received PBO + Pred-52. Of the 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving prednisone (median dosage 2.0 mg/day). Among 101 PBO + Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving prednisone (median dosage 5.0 mg/day). Many flares occurred while patients were taking >10 mg/day prednisone: 9 (25%) in the TCZ groups and 13 (22%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO + Pred-treated groups occurred with normal CRP levels. More than half of the PBO + Pred-treated patients had elevated CRP levels without flares. Benefits of the TCZ and prednisone combination over prednisone alone for remission induction were apparent by 8 weeks., Conclusion: Most GCA flares occurred while patients were still receiving prednisone. Acute-phase reactant levels were not reliable indicators of flare in patients treated with TCZ plus prednisone or with prednisone alone. The addition of TCZ to prednisone facilitates earlier GCA control., (© 2019 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

We have reported the existence of a distinct neutrophil phenotype in giant cell arteritis (GCA) patients arising at week 24 of steroid treatment. In the present study, we investigated whether longitudinal analysis of neutrophil phenotype in patients with polymyalgia rheumatica (PMR) could reveal a novel association with disease status and immune cell cross-talk. Thus, we monitored PMR patient neutrophil phenotype and plasma microvesicle (MV) profiles in blood aliquots collected pre-steroid, and then at weeks 1, 4, 12 and 24 post-steroid treatment.Using flow cytometric and flow chamber analyses, we identified 12-week post-steroid as a pivotal time-point for a marked degree of neutrophil activation, correlating with disease activity. Analyses of plasma MVs indicated elevated AnxA1+ neutrophil-derived vesicles which, in vitro , modulated T-cell reactivity, suggesting distinct neutrophil phenotypic and cross-talk changes at 24 weeks, but not at 12-week post-steroid.Together, these data indicate a clear distinction from GCA patient neutrophil and MV signatures, and provide an opportunity for further investigations on how to 'stratify' PMR patients and monitor their clinical responses through novel use of blood biomarkers., (© 2019 The Author(s).)

GCA shares many clinical features with PMR and Takayasu arteritis. The current mainstay of therapy for all three conditions is glucocorticoid therapy. Given the chronic, relapsing nature of these conditions and the morbidity associated with glucocorticoid therapy, there is a need for better treatment options to induce and sustain remission with fewer adverse effects. Conventional immunosuppressive treatments have been studied and have a modest effect. There is a keen interest in biologic therapies with studies showing the efficacy of IL-6 antagonists in PMR and GCA. Recently the first two randomized clinical trials in Takayasu arteritis have been completed. A major challenge for all of these conditions is the lack of standardized measures to assess disease activity. Long-term studies are needed to evaluate the impact of biologic therapies showing potential on important clinical outcomes such as vascular damage, cost-effectiveness and quality of life. The optimal duration of treatment also needs to be assessed.

Glucocorticoids are the mainstay of treatment for GCA. Patients often require long-term treatment that may be associated with numerous adverse effects, depending on the dose and the duration of treatment. Trends in recent decades for glucocorticoid use in GCA suggest increasing cumulative doses and longer exposures. Common adverse events (AEs) reported in glucocorticoid-treated GCA patients include osteoporosis, hypercholesterolaemia, hypertension, posterior subcapsular cataract, infections, diabetes mellitus, Cushingoid appearance, adrenal insufficiency and aseptic necrosis of bone. AEs considered most worrisome by patients and rheumatologists include weight gain, psychological effects, osteoporosis, cardiometabolic complications and infections. The challenge is to maximize the benefit-risk ratio by giving the maximum glucocorticoid treatment necessary to control GCA initially and then to prevent relapse but to give the minimum treatment possible to avoid glucocorticoid-related AEs. We discuss the safety issues associated with long-term glucocorticoid use in patients with GCA and strategies for preventing glucocorticoid-related morbidity.

Objective: A feasibility study to assess efficacy and safety of modified release (MR) prednisone (Lodotra™) compared to immediate release (IR) prednisolone in patients with newly diagnosed giant cell arteritis (GCA)., Methods: Twelve patients with new diagnosis of GCA were initially treated with high-dose prednisolone (40-60 mg) daily for 4 weeks and then randomized to two open arms to continue tapering steroid treatment with either standard IR prednisolone or MR prednisone. Patients were reviewed every 2 weeks either face to face or by telephone, for a total of 26 weeks. Disease activity, steroid-related side effects, sleep disturbance, fatigue scores and blood tests were systematically monitored. The primary endpoint (efficacy) was defined as the proportion of patients achieving persistent clinical disease control (without features of active disease and remaining flare free at 26 weeks) in each arm., Results: At 26 weeks, 6/7 patients taking MR prednisone were in persistent control, compared with 4/5 receiving IR prednisone. One patient in each group suffered a disease flare necessitating an increased steroid dose. There were no statistically significant differences between the groups in terms of reduction in inflammatory markers, Health Assessment Questionnaire, visual analogue scale, fatigue and improvement in EuroQol 5D scores., Conclusion: This trial shows that MR prednisone appears to be a safe and effective treatment for GCA with a similar outcome profile to standard IR prednisolone., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis., Methods: In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone and safety were also assessed., Results: Sustained remission at week 52 occurred in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P<0.001 for the comparisons of either active treatment with placebo). The cumulative median prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as compared with 3296 mg in the placebo group that underwent the 26-week taper (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred in 15% of the patients in the group that received tocilizumab weekly, 14% of those in the group that received tocilizumab every other week, 22% of those in the placebo group that underwent the 26-week taper, and 25% of those in the placebo group that underwent the 52-week taper. Anterior ischemic optic neuropathy developed in one patient in the group that received tocilizumab every other week., Conclusions: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01791153 .).

Objective: To report entry criteria and clinical features of patients with newly diagnosed and relapsing giant cell arteritis (GCA) enrolled in a randomized trial of tocilizumab, an interleukin-6 receptor-alpha inhibitor., Methods: Newly diagnosed GCA was defined as diagnosis ≤6 weeks before baseline. Relapsing GCA was defined as diagnosis >6 weeks before baseline with ≥2 consecutive weeks of prednisone ≥40mg/day. All patients had active GCA within 6 weeks of baseline. All statistical results are exploratory., Results: Of 251 patients, 119 (47%) had newly diagnosed and 132 (53%) had relapsing GCA. Mean age was 69 years in both subsets; 75% were women. Relapsing patients were heavier [difference in means (95% CI): women, 4.18kg (0.49-7.87, P = 0.027); men, 8.25kg (1.42-15.09, P = 0.019)] and had higher mean body mass index [difference in means (95% CI): women, 1.72kg/m 2 (0.44-2.99, P = 0.009); men, 2.85kg/m 2 (0.3 2 -5.37, P = 0.028)]. Relapsers had higher baseline prevalence of depression (16% vs. 4%) and osteopenia/osteoporosis (33% vs. 23%, P = 0.002 and P = 0.062, respectively). At diagnosis, 67% had new-onset headaches; 34% had mouth pain/jaw claudication. One-fifth had polymyalgia rheumatica symptoms but no cranial manifestations; 62% had positive temporal artery biopsy findings; 37% were enrolled on the basis of cross-sectional imaging study findings., Conclusions: Demographics of the GiACTA population reflect the epidemiologic profile of GCA. Baseline comorbidities associated with glucocorticoids were more prevalent among relapsing patients than among those with newly diagnosed disease, highlighting the need for new GCA treatment options. More than one-third of patients were enrolled based on large-vessel imaging., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Importance: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are related inflammatory disorders occurring in persons aged 50 years and older. Diagnostic and therapeutic approaches are heterogeneous in clinical practice., Objective: To summarize current evidence regarding optimal methods for diagnosing and treating PMR and GCA., Evidence Review: MEDLINE, EMBASE, and Cochrane databases were searched from their inception dates to March 30, 2016. Screening by 2 authors resulted in 6626 abstracts, of which 50 articles met the inclusion criteria. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool or American College of Cardiology Foundation/American Heart Association methodology., Findings: Twenty randomized clinical trials for therapy (n = 1016 participants) and 30 imaging studies for diagnosis and/or assessing response to therapy (n = 2080 participants) were included. The diagnosis of PMR is based on clinical features such as new-onset bilateral shoulder pain, including subdeltoid bursitis, muscle or joint stiffness, and functional impairment. Headache and visual disturbances including loss of vision are characteristic of GCA. Constitutional symptoms and elevated inflammatory markers (>90%) are common in both diseases. Ultrasound imaging enables detection of bilateral subdeltoid bursitis in 69% of PMR patients. In GCA, temporal artery biopsy remains the standard for definitive diagnosis. Ultrasound and magnetic resonance imaging (MRI) of large vessels revealing inflammation-induced wall thickening support the diagnosis of GCA (specificity 78%-100% for ultrasound and 73%-97% for MRI). Glucocorticoids remain the primary treatment, but the optimal initial dose and tapering treatment regimens are unknown. According to consensus-based recommendations, initial therapy for PMR is prednisone, 12.5 to 25 mg/day or equivalent, and 40 to 60 mg/day for GCA, followed by individualized tapering regimens in both diseases. Adjunctive methotrexate may reduce cumulative glucocorticoid dosage by 20% to 44% and relapses by 36% to 54% in both PMR and GCA. Use of tocilizumab as additional treatment with prednisone showed a 2- to 4-fold increase in remission rates of GCA in a randomized clinical trial (N = 30)., Conclusions and Relevance: Diagnosis of PMR/GCA is made by clinical features and elevated inflammatory markers. In PMR, ultrasound imaging may improve diagnostic accuracy. In GCA, temporal artery biopsy may not be required in patients with typical disease features accompanied by characteristic ultrasound or MRI findings. Consensus-based recommendations suggest glucocorticoids as the most effective therapy for PMR/GCA. Methotrexate may be added to glucocorticoids in patients at risk for relapse and in those with glucocorticoid-related adverse effects or need for prolonged glucocorticoid therapy.

There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term glucocorticoid therapy was often lacking since relevant study results were often either missing, contradictory or carried a high risk of bias. The group agreed that the risk of harm is low for the majority of patients at long-term dosages of ≤5 mg prednisone equivalent per day, whereas at dosages of >10 mg/day the risk of harm is elevated. At dosages between >5 and ≤10 mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends on both dose and patient-specific parameters. General and glucocorticoid-associated risk factors and protective factors such as a healthy lifestyle should be taken into account when evaluating the actual and future risk., (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/)

Diagnosis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) is based on typical clinical, histologic, and laboratory features. Ultrasonographic imaging in PMR with assessment especially of subdeltoid bursitis can aid in diagnosis and in following response to treatment. In GCA, diagnosis and disease activity are supported with ultrasonographic, MRI, or [(18)F]fluorodeoxyglucose PET evaluation of large vessels. Glucocorticoids are the primary therapy for PMR and GCA. Methotrexate may be used in patients at high risk for glucocorticoid adverse effects and patients with frequent relapse or needing protracted therapy. Other therapeutic approaches including interleukin 6 antagonists are under evaluation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease in persons over the age of 50 years. There are many diseases which mimic PMR, for which reason a careful diagnostic approach is required. While it is thought to be exquisitely responsive to glucocorticosteroid therapy, many patients respond incompletely and/or develop serious side effects over the protracted disease course. Improved methods for classification and disease assessment together with standardized treatment approaches and outcome assessments can serve to improve the care of patients with this disease.

Giant cell arteritis (GCA) is a large-vessel vasculitis predominantly affecting older people, with a peak incidence between 70 and 79 years of age. If untreated, ischaemic complications can be catastrophic for the patient, including blindness. We review the current treatment paradigms for this condition, the mainstay of which is immediate high-dose glucocorticoid therapy with a gradual dose tapering. Adverse events of glucocorticoid therapy are often observed after 12-24 months and corticosteroid-sparing adjuvant therapies are used in severe disease, multiple flares or patients at high risk of prolonged therapy. The current understanding of the pathogenesis of GCA is explored. This has informed the identification of new potential targets and approaches to treatment. Blockade of interleukin (IL)-6 (tocilizumab) and IL-1 (gevokizumab) are being evaluated in phase III clinical trials. It is hoped that improved risk stratification of organ damage and relapses will be developed using imaging and biomarkers, allowing for individualised treatment for patients; however, there remains further work to be done before this becomes a reality.

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are characterised by systemic inflammation and critical ischaemia. GCA is a medical emergency. Neuro-ophthalmic complications occur early, with permanent vision loss in up to a fifth of patients, resulting mainly from failure of prompt recognition and treatment. Diagnosis of large vessel vasculitis is often delayed due to poor recognition of early, often non-specific symptoms. Laboratory inflammatory markers are often discordant with disease activity. Modern imaging techniques show promise in diagnosis and disease monitoring, improving our understanding of major artery involvement in large vessel vasculitis. However, in practice, their role is still unclear. The mainstay of therapy remains corticosteroids. Experience using conventional disease-modifying drugs is mixed, and biological therapies require further evaluation for their steroid-sparing potential.

Objectives To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. Methods An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. Results In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. Conclusion This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials. [ABSTRACT FROM AUTHOR]

Objective Tocilizumab plus prednisone induces sustained glucocorticoid-free remission in patients with GCA. However, its long-term benefits in new-onset vs relapsing disease are uncertain, and the value of weekly vs every-other-week dosing has not been evaluated. Methods In Giant-Cell Arteritis Actemra (GiACTA) part 1, patients with new-onset or relapsing GCA received blinded tocilizumab weekly (TCZ QW), tocilizumab every-other-week (TCZ Q2W) or placebo for 52 weeks, with a prednisone taper. In part 2 (open-label), patients were treated at investigator discretion for 104 weeks. In this analysis, patients were evaluated according to their original treatment assignments, and outcomes beyond 52 weeks were assessed. Outcomes of interest included time to first flare and cumulative glucocorticoid exposure over 3 years according to baseline disease status. Results Part 1 enrolled 250 patients; 215 entered part 2. At baseline, 48% had new-onset disease and 52% had relapsing disease. In patients with new-onset and relapsing disease, the median time to first flare in the TCZ QW group was 577 and 575 days, respectively, vs 479 and 428 days with TCZ Q2W and 179 and 224 days with placebo; the median cumulative glucocorticoid dose was 3068 mg and 2191 mg with TCZ QW, 4080 mg and 2353 mg with TCZ Q2W, and 4639 mg and 6178 mg with placebo. Conclusion TCZ QW delayed the time to flare and reduced the cumulative glucocorticoid dose in patients with relapsing GCA and new-onset GCA. These data support initiating TCZ QW as part of first-line therapy in all patients with active GCA. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT01791153. [ABSTRACT FROM AUTHOR]

Objectives: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in pathogenesis of giant cell arteritis. We evaluated the efficacy of the GM-CSF receptor antagonist mavrilimumab in maintaining disease remission.Methods: This phase 2, double-blind, placebo-controlled trial enrolled patients with biopsy-confirmed or imaging-confirmed giant cell arteritis in 50 centres (North America, Europe, Australia). Active disease within 6 weeks of baseline was required for inclusion. Patients in glucocorticoid-induced remission were randomly assigned (3:2 ratio) to mavrilimumab 150 mg or placebo injected subcutaneously every 2 weeks. Both groups received a 26-week prednisone taper. The primary outcome was time to adjudicated flare by week 26. A prespecified secondary efficacy outcome was sustained remission at week 26 by Kaplan-Meier estimation. Safety was also assessed.Results: Of 42 mavrilimumab recipients, flare occurred in 19% (n=8). Of 28 placebo recipients, flare occurred in 46% (n=13). Median time to flare (primary outcome) was 25.1 weeks in the placebo group, but the median was not reached in the mavrilimumab group (HR 0.38; 95% CI 0.15 to 0.92; p=0.026). Sustained remission at week 26 was 83% for mavrilimumab and 50% for placebo recipients (p=0.0038). Adverse events occurred in 78.6% (n=33) of mavrilimumab and 89.3% (n=25) of placebo recipients. No deaths or vision loss occurred in either group.Conclusions: Mavrilimumab plus 26 weeks of prednisone was superior to placebo plus 26 weeks of prednisone for time to flare by week 26 and sustained remission in patients with giant cell arteritis. Longer treatment is needed to determine response durability and quantify the glucocorticoid-sparing potential of mavrilimumab.Trial Registration Number: ClinicalTrials.gov number: NCT03827018, Europe (EUdraCT number: 2018-001003-36), and Australia (CT-2018-CTN-01 865-1). [ABSTRACT FROM AUTHOR]

Objectives This systematic review and meta-analysis aimed to evaluate the diagnostic value of the halo sign in the assessment of GCA. Methods A systematic literature review was performed using MEDLINE, EMBASE and Cochrane central register databases up to August 2020. Studies informing on the sensitivity and specificity of the US halo sign for GCA (index test) were selected. Studies with a minimum of five participants were included. Study articles using clinical criteria, imaging such as PET-CT and/or temporal artery biopsy (TAB) as the reference standards were selected. Meta-analysis was conducted with a bivariate model. Results The initial search yielded 4023 studies. Twenty-three studies (patients n  = 2711) met the inclusion criteria. Prospective (11 studies) and retrospective (12 studies) studies in academic and non-academic centres were included. Using clinical diagnosis as the standard (18 studies) yielded a pooled sensitivity of 67% (95% CI: 51, 80) and a specificity of 95% (95% CI: 89, 98%). This gave a positive and negative likelihood ratio for the diagnosis of GCA of 14.2 (95% CI: 5.7, 35.5) and 0.375 (95% CI: 0.22, 0.54), respectively. Using TAB as the standard (15 studies) yielded a pooled sensitivity of 63% (95% CI: 50, 75) and a specificity of 90% (95% CI: 81, 95). Conclusion The US halo sign is a sensitive and specific approach for GCA assessment and plays a pivotal role in diagnosis of GCA in routine clinical practice. Registration PROSPERO 2020 CRD42020202179. [ABSTRACT FROM AUTHOR]

Objectives To compare the ultrasound characteristics with clinical features, final diagnosis and outcome; and to evaluate the halo size following glucocorticoid treatment in patients with newly diagnosed GCA. Methods Patients with suspected GCA, recruited from an international cohort, had an ultrasound of temporal (TA) and axillary (AX) arteries performed within 7 days of commencing glucocorticoids. We compared differences in clinical features at disease presentation, after 2 weeks and after 6 months, according to the presence or absence of halo sign. We undertook a cross-sectional analysis of the differences in halo thickness using Pearson's correlation coefficient (r) and Analysis of Variance (ANOVA). Results A total of 345 patients with 6 months follow-up data were included; 226 (65.5%) had a diagnosis of GCA. Jaw claudication and visual symptoms were more frequent in patients with halo sign (P  =0.018 and P  =0.003, respectively). Physical examination abnormalities were significantly associated with the presence of ipsilateral halo (P  <0.05). Stenosis or occlusion on ultrasound failed to contribute to the diagnosis of GCA. During 7 days of glucocorticoid treatment, there was a consistent reduction in halo size in the TA (maximum halo size per patient: r =−0.30, P  =0.001; and all halos r =−0.23, P  <0.001), but not in the AX (P  >0.05). However, the presence of halo at baseline failed to predict future ischaemic events occurring during follow-up. Conclusion In newly diagnosed GCA, TA halo is associated with the presence of ischaemic features and its size decreases following glucocorticoid treatment, supporting its early use as a marker of disease activity, in addition to its diagnostic role. [ABSTRACT FROM AUTHOR]

Objectives: To measure serial interleukin (IL)‐6 levels in newly diagnosed patients with giant cell arteritis (GCA), treated in a randomized controlled trial of modified‐release prednisone (MR) vs immediate‐release prednisolone (IR) used in a tapering regimen conforming to British Society for Rheumatology GCA guidelines. Methods: Patients (n = 12) were randomized into 2 treatment arms (7 MR, 5 IR) and followed over 26 weeks. We measured IL‐6 with additional markers. Results: A significantly higher overall mean IL‐6 level (P < .05) was seen in IR (mean = 12.15, standard error [SE] = 1.90) compared with MR (mean = 4.39, SE = 1.84). Mean collagen type 1 cross‐linked C‐telopeptide (CTX) concentration was significantly higher (P <.05) in both groups at week 4 (mean = 0.29, SE = 0.04) compared with week 26 (mean = 0.13, SE = 0.02). MR patients had adrenocorticotropic hormone (ACTH) suppression compared with IR (P < .05) throughout without differences in cortisol levels (P = .34). No significant differences were seen between arms in other markers. Conclusion: Our study suggests that elevated levels of IL‐6 in new GCA are better suppressed by MR prednisone compared with IR prednisolone. CTX was significantly reduced in both treatment arms indicating early metabolic effect of glucocorticoids on bone. ACTH suppression with MR prednisone may reflect a greater impact on the hypothalamic‐pituitary‐adrenal axis although cortisol was not affected. MR prednisone warrants further investigation in GCA. [ABSTRACT FROM AUTHOR]

The article discusses updates on giant cell arteritis (GCA) treatment and management. Topics explored include the approval of tocilizumab (TCZ) by the British National Institute for Health and Care Excellence (NICE) and National Health Service (NHS) England for treating patients with GCA, the clinical guidelines for GCA diagnosis, and the challenges associated with disease activity assessment during therapeutic administration of TCZ.

The author discusses development of research regarding therapies for treatment of large vessel vasculitis (LVV). Topics discussed include illustration of stages involved in disease progression, observation of high-dose glucocorticoids (GC) as mainstay in LVV treatment, utilization of Methotrexate as adjunctive therapy leads to reduction in GC exposure, involvement of Leflunomide as steroid-sparing for treatment of giant cell arteritis (GCA) and elucidation of Abatacept as anti-T cell therapy.

Objective We present 13 patients with retroperitoneal fibrosis, focusing on clinical features, radiological characteristics, treatments and their outcomes. Methods Retrospective review of the medical records was performed of all retroperitoneal fibrosis patients diagnosed and treated in our department between 2012 and 2017. Results Twelve patients were male, with a median age of 64 years. Eleven patients presented with abdominal pain or back pain or both. Aetiologies varied from idiopathic to malignancy and vasculitis. Twelve patients had PET scans. These showed 18F-fluorodeoxyglucose-avid retroperitoneal soft tissue around the abdominal aorta in the vast majority, with five scans also demonstrating localized or generalized uptake by the aorta. In all cases except one, glucocorticoids were applied as the first-line therapy. Further immunosuppressive therapy was required in 10 cases. Conclusion Our patients were male and older in age compared with the existing literature. PET scans were very helpful in diagnosis of retroperitoneal fibrosis. Rituximab was found to be an effective treatment in six of our patients. [ABSTRACT FROM AUTHOR]

BACKGROUND More than half of patients with polymyalgia rheumatica have a relapse during tapering of glucocorticoid therapy. Previous studies have suggested that interleukin-6 blockade may be clinically useful in the treatment of polymyalgia rheumatica. Sarilumab, a human monoclonal antibody, binds interleukin-6 receptor α and efficiently blocks the interleukin-6 pathway. METHODS In this phase 3 trial, we randomly assigned patients in a 1:1 ratio to receive 52 weeks of a twice-monthly subcutaneous injection of either sarilumab (at a dose of 200 mg) plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. The primary outcome at 52 weeks was sustained remission, which was defined as the resolution of signs and symptoms of polymyalgia rheumatica by week 12 and sustained normalization of the C-reactive protein level, absence of disease flare, and adherence to the prednisone taper from weeks 12 through 52. RESULTS A total of 118 patients underwent randomization (60 to receive sarilumab and 58 to receive placebo). At week 52, sustained remission occurred in 28% (17 of 60 patients) in the sarilumab group and in 10% (6 of 58 patients) in the placebo group (difference, 18 percentage points; 95% confidence interval, 4 to 32; P=0.02). The median cumulative glucocorticoid dose at 52 weeks was significantly lower in the sarilumab group than in the placebo group (777 mg vs. 2044 mg; P<0.001). The most common adverse events with sarilumab as compared with placebo were neutropenia (15% vs. 0%), arthralgia (15% vs. 5%), and diarrhea (12% vs. 2%). More treatment-related discontinuations were observed in the sarilumab group than in the placebo group (12% vs. 7%). CONCLUSIONS Sarilumab showed significant efficacy in achieving sustained remission and reducing the cumulative glucocorticoid dose in patients with a relapse of polymyalgia rheumatica during glucocorticoid tapering. (Funded by Sanofi and Regeneron Pharmaceuticals; SAPHYR ClinicalTrials.gov number, NCT03600818. opens in new tab.) [ABSTRACT FROM AUTHOR]