The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

Extended ultrasound examination identifies more large vessel involvement in patients with giant cell arteritis.

OBJECTIVES: To compare limited with a more extended ultrasound examination (anteromedial ultrasound, A2-ultrasound) to detect large vessel (LV) involvement in patients with newly diagnosed GCA. METHODS: Patients with new-onset GCA were included at the time of diagnosis. All patients were examined using limited ultrasound (ultrasound of the axillary artery as visualized in the axilla) and an extended A2-ultrasound method (which also includes the carotid, vertebral, subclavian and proximal axillary arteries), in addition to temporal artery ultrasound. RESULTS: One hundred and thirty-three patients were included in the study. All patients fulfilled the criteria according to a proposed extension of the 1990 ACR classification criteria for GCA and had a positive ultrasound examination at diagnosis. Ninety-three of the 133 GCA patients (69.9%) had LV involvement when examined by extended A2-ultrasound, compared with only 56 patients (42.1%) by limited ultrasound (P < 0.001). Twelve patients (9.0%) had vasculitis of the vertebral arteries as the only LVs involved. Five patients (3.8%) would have been missed as having GCA if only limited ultrasound was performed. Forty patients (30.0%) had isolated cranial GCA, 21 patients (15.8%) had isolated large vessel GCA and 72 patients (54.1%) had mixed-GCA. CONCLUSION: Extended A2-ultrasound examination identified more patients with LV involvement than the limited ultrasound method. However, extended A2-ultrasound requires high expertise and high-end equipment and should be performed by ultrasonographers with adequate training.

Exploring the impact of the national tender system on the use of costly drugs treating rheumatoid arthritis patients in ten rheumatology centers in Norway (2010-2019).

BACKGROUND: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019. METHOD: The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described. RESULT: The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively. CONCLUSION: Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks.

Exploring drug cost and disease outcome in rheumatoid arthritis patients treated with biologic and targeted synthetic DMARDs in Norway in 2010-2019 - a country with a national tender system for prescription of costly drugs.

BACKGROUND: In Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system. METHODS: RA patients monitored in ordinary clinical practice were recruited from 10 Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process. RESULTS: The number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39% in 2010 and 45% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 42 to 67%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47%, from 13.1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75% (13.0 thousand EUR in 2010 and 3.2 thousand EUR in 2019). CONCLUSIONS: In the period 2010-2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities' intention to reduce treatment costs by implementing a tender system has been successful.

Diagnosing giant cell arteritis: a comprehensive practical guide for the practicing rheumatologist.

GCA is the most common large vessel vasculitis in the elderly population. In recent years, advanced imaging has changed the way GCA can be diagnosed in many locations. The GCA fast-track clinic approach combined with US examination allows prompt treatment and diagnosis with high certainty. Fast-track clinics have been shown to improve prognosis while being cost effective. However, all diagnostic modalities are highly operator dependent, and in many locations expertise in advanced imaging may not be available. In this paper, we review the current evidence on GCA diagnostics and propose a simple algorithm for diagnosing GCA for use by rheumatologists not working in specialist centres.

A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.

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

Early variation of ultrasound halo sign with treatment and relation with clinical features in patients with giant cell arteritis.

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.

EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice summary.

Large vessel vasculitis (LVV) is the most common form of primary vasculitis comprising of giant cell arteritis (GCA), Takayasu's arteritis (TAK) and idiopathic aortitis. Early diagnosis and treatment of LVV are paramount to reduce the risk of ischemic complications such as visual loss and strokes, vascular stenosis and occlusion, and aortic aneurysm formation. Use of imaging modalities [ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT) and [18F]-fluorodeoxyglucose positron emission tomography (PET)] has steadily increased to enable assessment of cranial and extracranial arteries, as well as the aorta. These imaging modalities are less invasive, more sensitive and readily available compared to temporal artery biopsy (TAB). Modern imaging methods have changed the role of TAB in diagnosing GCA and have replaced diagnostic angiography. Over the last two decades, several studies have evaluated the use of US, MRI, CT and PET in LVV. However, these various imaging tools are not yet uniformly used in routine clinical practice and controversy exists as to which imaging modality best provides meaningful assessments of disease activity and damage in LVV. In January 2018, evidence-based recommendations for the use of imaging modalities in LVV were published. The aim of this review is to summarize the current evidence of imaging in patients with or suspected of having LVV, and to highlight the clinical implications of the EULAR recommendations.

A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility.

We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10(-40), OR = 1.73). A multivariate model including class II amino acids of HLA-DRß1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1(∗)04. An omnibus test on polymorphic amino acid positions highlighted DRß1 13 (p = 4.08 × 10(-43)) and HLA-DQα1 47 (p = 4.02 × 10(-46)), 56, and 76 (both p = 1.84 × 10(-45)) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10(-6), OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10(-6), OR = 1.20), and REL (rs115674477, p = 1.10 × 10(-5), OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function.

EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice.

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

The proposed role of ultrasound in the management of giant cell arteritis in routine clinical practice.

Objective: To develop and explore a protocol for using colour duplex sonography (CDS) in the routine care of GCA. Methods: We tested CDS of temporal arteries and axillary arteries (AXs) on consecutive patients with suspected or established GCA, between July 2014 and September 2016. Results: We assessed 293 patients [age 72 (10), female/male 196/97], of whom 118 had clinically confirmed GCA. Seventy-three percent of patients had already received high-dose glucocorticoids (GCs) for 17 (33) days. Among new referrals with <7 days of GC treatment (n = 55), the sensitivity of CDS was 63.3% (95% CI: 44%, 80%), specificity 100% (95% CI: 83%, 100%), positive predictive value 100% and negative predictive value 64.5% (95% CI: 53%, 74%). Sensitivity rose to 81.8% in patients with jaw claudication and high inflammatory markers. During the observation period, the rate of temporal artery biopsies decreased from 72 (42%) to 36 (25%) (P = 0.002). CDS was positive in 21% of 89 follow-up scans in asymptomatic individuals, compared with 37% in patients experiencing clinical flares. Over time, the number of halos reduced; only new or flaring patients showed a halo in four or more sites. The diameter of axillary halos reduced from referral [1.6 (0.4) mm] to follow-up [1.4 (0.2) mm, P = 0.01] or flares [1.4 (0.2) mm, P = 0.02]. Conclusion: CDS provides high positive predictive value for diagnosing GCA and allows for a significant reduction in temporal artery biopsies. We explored the role of CDS in detecting flares and demonstrated a relationship to the extent of the distribution of halos, but not to their size.

The use of ultrasound to assess giant cell arteritis: review of the current evidence and practical guide for the rheumatologist.

Colour duplex sonography (CDS) of temporal arteries and large vessels is an emerging diagnostic tool for GCA. CDS can detect wall oedema, known as a halo, throughout the length of the vessel and shows higher sensitivity compared with biopsy. Specificity reaches 100% in case of bilateral halos. A positive compression sign has been demonstrated to be a robust marker with excellent inter-observer agreement. The assessment of other large vessels, particularly the axillary arteries, is recognized to further increase the sensitivity and to reliably represent extra-cranial involvement in other areas. Nevertheless, CDS use is still not widespread in routine clinical practice and requires skilled sonographers. Moreover, its role in the follow-up of patients still needs to be defined. The aim of this review is to provide the current evidence and technical parameters to support the rheumatologist in the CDS evaluation of patients with suspected GCA.

Ultrasonographic evaluation in psoriatic arthritis is of major importance in evaluating disease activity.

OBJECTIVE: To investigate the association between clinical and ultrasonographic (US) evidence of inflammation in psoriatic arthritis (PsA), as well as to compare clinical and US remission criteria. METHODS: In this cross-sectional study 141 PsA outpatients were included. Minimal disease activity (MDA), 28-joint Disease Activity Score (DAS28), Disease Activity Index for PSoriatic Arthritis (DAPSA) and modified versions of Composite Psoriatic Disease Activity Index (CPDAI) and Psoriatic ArthritiS Disease Activity Score (PASDAS) were assessed. Remission criteria were explored. US evaluation was performed on 34 joints, in addition to joints being tender/swollen by 66/68 joint count, 30 tendons, 10 entheses and additionally entheses found to be tender by clinical examination of 19 other entheses. Power Doppler (PD) and grey scale global scores on joints, entheses and tendons were assessed. US remission was defined as no PD activity in joints, entheses and tendons. RESULTS: DAPSA and DAS28, but not CPDAI and PASDAS, were associated with PD activity. MDA was fulfilled in 22.7% and the clinical remission criteria in 5.7%-9.9% of the patients. US remission was found in 49.6% of the patients. The prevalence of PD activity at joints, entheses and tendons was similar for patients fulfilling versus not fulfilling MDA/clinical remission criteria. MDA (OR 2.3, p=0.048), DAPSA ≤3.3 (OR 4.2, p=0.025) and Boolean's (OR=7.8, p=0.033) definitions of remission were found to predict US remission. CONCLUSIONS: We found major discrepancies between US and clinical findings. DAPSA and DAS28 reflected US findings better than CPDAI and PASDAS. MDA, DAPSA and Boolean's remission criteria predicted US remission.

The fast-track ultrasound clinic for early diagnosis of giant cell arteritis significantly reduces permanent visual impairment: towards a more effective strategy to improve clinical outcome in giant cell arteritis?

OBJECTIVE: Permanent visual impairment has been reported to occur in up to 19% of GCA patients. The aim of this study was to examine whether implementation of a fast-track approach could reduce the rate of permanent visual impairment and inpatient days of care in GCA patients. METHODS: A fast-track outpatient GCA clinic (FTC) was implemented in the Department of Rheumatology, Hospital of Southern Norway Trust Kristiansand, Norway in 2012. The patients included in this study were subsequently recruited between March 2010 and October 2014. Routine clinical and laboratory data and number of inpatient days of care were collected. RESULTS: During the observation period, 75 patients were diagnosed with GCA. Among the 75 GCA patients, 32 were evaluated conventionally and 43 in the FTC. In the conventionally approached group, six patients suffered from permanent visual impairment, while in the FTC group only one patient suffered from permanent visual impairment. The relative risk of permanent visual impairment in the GCA patients examined in the FTC was 88% lower compared with the conventionally evaluated group (relative risk 0.12, 95% CI: 0.01, 0.97, P = 0.01). The mean difference in inpatient days of care between patients evaluated conventionally and patients evaluated in the FTC was 3 days (3.6 vs 0.6 days, P < 0.0005). CONCLUSION: The implementation of the FTC in GCA care appears to significantly reduce the risk of permanent visual impairment and is more cost effective by reducing the need for inpatient care.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

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

Vascular ultrasound as a follow-up tool in patients with giant cell arteritis: a prospective observational cohort study.

Objectives: To evaluate relapses in giant cell arteritis (GCA), investigate the utility of vascular ultrasound to detect relapses, and develop and assess a composite score for GCA disease activity (GCAS) based on clinical symptoms, ultrasound imaging activity, and C-reactive protein (CRP). Methods: Patients with GCA were prospectively followed with scheduled visits, including assessment for clinical relapse, protocol ultrasound examination, and CRP. At each visit, patients were defined as having ultrasound remission or relapse. GCAS was calculated at every visit. Results: The study included 132 patients, with a median follow-up time of 25 months [interquartile range (IR) 21]. The clinical relapse rate was 60.6%. There were no differences in relapse rates between GCA subtypes (cranial-GCA, large vessel (LV)-GCA, and mixed-GCA) (p = 0.83). Ultrasound yielded a sensitivity of 61.2% and a specificity of 72.3% for diagnosing GCA- relapse in our cohort. In 7.7% of follow-up visits with clinical relapses, neither high CRP nor findings of ultrasound relapse were registered. In comparison, in 10.3% of follow-up visits without symptoms of clinical relapse, there were both a high CRP and findings of ultrasound relapse. Conclusion: We found moderate sensitivity and specificity for ultrasound as a monitoring tool for relapse in this prospective cohort of GCA patients. The extent or subtype of vasculitis at the diagnosis did not influence the number of relapses. Based on a combination of clinical symptoms, elevated CRP, and ultrasound findings, a composite score for GCA activity is proposed.

Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study.

BACKGROUND: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. METHODS: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. FINDINGS: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10-8; OR 1·19 [95% CI 1·12-1·26]) and VTN (rs704; p=2·75 × 10-9; OR 0·84 [0·79-0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10-8; OR 1·18 [1·12-1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15-3·82]; p=1·73 × 10-13). INTERPRETATION: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis. FUNDING: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Research.