OBJECTIVES:In the SELECT-GCA trial, upadacitinib 15 mg/d was associated with higher rates of disease remission and reduced glucocorticoid exposure vs placebo in patients with giant cell arteritis (GCA) through 1 year. This study evaluated the clinical impact of upadacitinib continuation vs withdrawal through 2 years. METHODS:In period 1 of SELECT-GCA, patients aged ≥50 years were randomised 2:1:1 to oral upadacitinib 15 mg or 7.5 mg with a 26-week glucocorticoid taper or placebo with a 52-week taper. In period 2 (52-week re-randomised, blinded extension), patients achieving ≥24 weeks of consecutive remission by week 52 were re-randomised 2:1 to continue upadacitinib or switch to placebo. Efficacy endpoints were assessed from weeks 52 to 104, and safety was evaluated over 2 years. All P values are nominal. RESULTS:Among 103 patients receiving upadacitinib 15 mg who achieved ≥24 weeks sustained remission and were re-randomised in period 2, 68 continued treatment and 35 switched to placebo at week 52. From weeks 52 to 104, patients continuing upadacitinib 15 mg vs switching to placebo experienced fewer disease flares (7.4% vs 59.5%; P ≤ .0001), greater maintenance of glucocorticoid-free remission (71.7% vs 31.4%; P ≤ .0001), and lower glucocorticoid exposure (median exposure: 0 mg vs 1048 mg; P ≤ .0001). Safety was generally similar between upadacitinib and placebo groups. No new clinically significant safety risks were identified with upadacitinib through 2 years, and safety remained consistent with the established profile. CONCLUSIONS:These data further support a favourable benefit-risk profile for extended use of upadacitinib 15 mg for treatment of GCA.

Abstract Background/Aims In the SELECT-GCA phase 3 trial, treatment of patients with giant cell arteritis (GCA) with upadacitinib 15 mg (UPA15) demonstrated superior rates of disease remission, fewer disease flares, and reduced glucocorticoid use compared with placebo. The current study analyzed the 2-year outcomes. Methods SELECT-GCA included a 52-week randomized, placebo-controlled period 1 and a 52-week randomized, blinded extension period 2. Patients aged ≥50 years with a diagnosis of active GCA were randomized (2:1:1) to UPA15 or upadacitinib 7.5 mg (UPA7.5) once daily with a 26-week glucocorticoid taper or placebo with a 52-week glucocorticoid taper. Period 2 involved patients in remission for ≥24 consecutive weeks before the week 52 visit. Patients originally randomized to UPA7.5 or UPA15 were re-randomized (2:1) to continue the same dose of UPA or to switch to placebo in period 2. Patients originally randomized to placebo continued placebo. Efficacy outcomes were evaluated through week 104 and included remission, disease flare-related endpoints, and cumulative glucocorticoid exposure. The safety analysis included all patients who received ≥1 dose of study drug in period 1 and continued the same treatment in period 2. Exposure-adjusted treatment-emergent adverse events (TEAEs) are reported through 2 years in this population. Results 181/428 patients (42%) achieved ≥24 consecutive weeks of sustained remission in period 1 and entered period 2 (placebo continuous, n = 34; UPA7.5 continuous, n = 30; UPA7.5 to placebo, n = 14; UPA15 continuous, n = 68; UPA15 to placebo, n = 35). Most (91%) of these patients completed the study, with 82% remaining on study drug. From week 52 through week 104, 67.3% of patients on continuous UPA15 maintained remission vs 28.6% who switched from UPA15 to placebo. Patients on continuous UPA15 showed a 90% reduction in risk of disease flare from week 52 through week 104 compared with those who switched from UPA15 to placebo. Safety was generally similar for UPA and placebo groups among patients who continued the same treatment in period 2. Rates of serious TEAEs were lower for both UPA doses than placebo. Compared to placebo, UPA15 showed lower rates of serious infections but higher rates of herpes zoster and elevated creatine kinase. One venous thromboembolism event occurred with UPA15 in a patient with multiple risk factors and none in the other treatment groups. No major adverse cardiovascular events or deaths occurred in period 2 in any treatment group. Conclusion For patients with GCA receiving UPA15, continued use of UPA in those who were in remission for ≥24 weeks during period 1, rather than switching to placebo, was associated with maintenance of remission and an approximately 1-gram reduction in the cumulative use of glucocorticoids in period 2. In this population, no new clinically significant safety risks were identified with use of UPA for 2 years. Disclosure W. Schmidt: Honoraria; Has received speaker fees/honoraria (includes speakers bureau, symposia, and expert witness) from Abbvie, Alfasigma, Amgen, Chugai, Eli Lilly, GlaxoSmithKline, Medac, Novartis, Pfizer, and UCB. Grants/research support; Has received grants/research support from AbbVie and Novartis. Other; Has been an advisor or review panel member for Abbvie, Boehringer Ingelheim, Fresenius Kabi, GlaxoSmithKline, and Novartis. A.R. Setty: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. C. Dejaco: Consultancies; Has received consultancy fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos, Sparrow, and Sanofi. Honoraria; Has received speaker fees/honoraria (includes speakers bureau, symposia, and expert witness) from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos, Sparrow, and Sanofi. A. Rubbert-Roth: Consultancies; Has received consultancy fees from AbbVie, Amgen, BMS, Boehringer, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, and Sanofi. Honoraria; Has received speaker fees/honoraria (includes speakers bureau, symposia, and expert witness) from AbbVie, Amgen, BMS, Boehringer, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, and Sanofi. M.C. Cid: Consultancies; Has received consultancy fees from GSK, AbbVie, CSL-Vifor, and AstraZeneca. Honoraria; Has received speaker fees/honoraria (includes speakers bureau, symposia, and expert witness) from GSK, CSL-Vifor, AbbVie, and AstraZeneca. Grants/research support; Has received a research grant from Kiniksa Pharmaceuticals and funding from Mininsterio de Ciencia e Innovación. T. Ishii: Consultancies; Has received consultancy fees from AbbVie, Asahi Kasei Pharma, Astellas, Ayumi Pharmaceutical, BMS, Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Ono Pharmaceutical, Pfizer, and Sanofi. A.D. Joshi: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. N. Zerad: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. A. Kadakia: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. S. Zhao: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. W. Zhao: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. I. Lagunes: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. C. Phillips: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. D. Blockmans: Consultancies; Has received consultant fees from GSK, Roche, AbbVie, and AstraZeneca. P.A. Merkel: Consultancies; Has received consultancy fees from AbbVie, Alpine, Amgen, ArGenx, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, CSL Behring, GlaxoSmithKline, iCell, Interius, Kinevant, Kyverna, Metagenomia, Neutrolis, Novartis, NS Pharma, Otsuka, Q32, Quell, Regeneron, Sanofi, Sparrow, Takeda, and Vistera. Shareholder/stock ownership; Has stock options or bond holdings for Kyverna, Q32, Lifordi, Neutrolis, and Sparrow. Grants/research support; Has received grant/research support from AbbVie, Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eicos, Electra, GlaxoSmithKline, Neutrolis, and Takeda.

BACKGROUND:Management of eosinophilic granulomatosis with polyangiitis (EGPA) is challenging due to inconsistent responses and frequent relapses with classic treatments. Mepolizumab (MPZ), an anti-interleukin-5 monoclonal antibody, has emerged as an effective treatment for patients with EGPA. This review assessed evidence of clinical outcomes and safety among patients with EGPA receiving MPZ in real-world settings. METHODS:A scoping review was conducted to identify real-world evidence on MPZ use in patients with EGPA. Relevant articles were identified in searches of OVID Medline and EMBASE databases alongside manual searches. RESULTS:Seventy-one references involving 51 original studies were selected for review. MPZ was administered at different dosages (predominantly 100 mg or 300 mg subcutaneously every 4 weeks) with a cumulative sample size of 2312 MPZ-treated patients. The mean duration of follow-up was 16.3 ± 9.7 months. Reported remission rates (mostly defined as a Birmingham Vasculitis Activity Score of 0 without or with low doses of glucocorticoids [GC]) ranged from 30.4% to 94.4% at 12-24 months. The overall reduction in relapse rates with MPZ ranged from 42% to 90.6%. The GC dose was significantly reduced after MPZ treatment (up to 87.2% at 16-18 months and 79.1% at 24-26 months). Approximately 50% of patients successfully discontinued GC usage at 12 months or more. No new safety signals were reported in real-world studies compared with the randomized controlled trials. CONCLUSIONS:In a real-world setting, MPZ treatment supported clinically significant benefits in patients with EGPA, with a very good safety profile.

OBJECTIVES:Treatment of GCA still requires substantial exposure to glucocorticoids (GCs), which are associated with significant toxicity. This study compares the efficacy and safety of the GC-only standard of care (SOC) with a regimen combining intravenous methylprednisolone (IVMP) pulses, MTX and lower doses of prednisone, in newly diagnosed patients with GCA. METHODS:A usual clinical practice study was conducted in three Spanish academic hospitals. One hundred and fifty-one patients diagnosed with GCA were treated with SOC prednisone (40-60 mg/d) or with IVMP (125-500 mg/d ×3) followed by lower-dose prednisone (≤30 mg/d) and MTX (IVMP/MTX), with a follow-up of 2 years. A propensity score was used to adjust for baseline differences in the multivariate analyses. RESULTS:Seventy-nine (52.3%) patients received SOC prednisone and 72 (47.7%) IVMP/MTX. The clinical characteristics at baseline were similar in both the groups. Hundred percent patients achieved remission after a median time of 4 weeks, without differences between the groups. Relapse rates were also similar. Patients receiving IVMP/MTX had significantly lower cumulative GC doses and reached prednisone ≤5 mg/d faster than SOC patients (mean 13.8 vs 56.5 weeks; P < 0.001). Patients in the IVMP/MTX group were less likely to suffer any GC-related adverse effect (adjusted OR 0.35, 95% CI 0.14-0.85; P = 0.021). CONCLUSIONS:The combination IVMP/MTX with lower-dose prednisone is as effective as the SOC in inducing remission and preventing relapses in GCA. The IVMP/MTX scheme significantly reduces GC exposure and GC-associated adverse effects. IVMP/MTX could be a potential GC-sparing strategy, especially in patients with GCA at higher risk of GC toxicity.

Objective : To identify the most important and relevant items to consider when developing criteria to measure response to treatment in giant cell arteritis (GCA). Methods : As part of an ongoing project to develop response criteria for GCA, a 4-round web-based Delphi exercise was conducted. Participants included patients with GCA and health professionals with expertise in GCA. Participants rated the importance (1=lowest, 9=highest) of 51 items selected based on a systematic literature review, grouped into six domains, and could suggest additional items. Items scored 7-9 by at least 70% of health professionals and 70% of patients were considered critically important and to have reached consensus. In the last round of the Delphi, participants ranked the top 10 most relevant items. A task force (n=32 members) meeting followed to review the Delphi results, discuss rankings, and finalize the selection of items. Results : One hundred eighty-seven physicians and 85 patients, from 38 countries, participated in the Delphi exercise. Twenty-four (75%) task force members participated in the virtual meeting. Thirteen new items were proposed in round 1. Twenty-four items were rated as critically important. No items were excluded during any round, and consensus was not reached for 40 items. The top 3 highest rated items by both patients and physicians were headache (ranked highest by 52%), amaurosis fugax (highest=10%), and jaw claudication (highest=7%). Twelve items were selected for the next phase of the project. Conclusion : Experts and patients identified 12 items considered important for measuring response to treatment in GCA.

OBJECTIVE:To compare fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging to clinical- and laboratory-based assessments of disease activity in a randomized controlled trial (RCT) in giant cell arteritis (GCA). METHODS:Patients with new-onset or relapsing GCA were randomized to guselkumab or placebo plus tapered glucocorticoids in an international, multicenter RCT. FDG-PET was performed at the baseline visit before randomization and repeated at disease flare or the week-52 visit (clinical remission off glucocorticoids). FDG-PET scans were interpreted as active or inactive by two readers, and the PET Vascular Activity Score was calculated to quantify arterial FDG uptake. FDG-PET findings were compared to clinical assessment, acute phase reactants, and glucocorticoid use at each visit. RESULTS:Baseline FDG-PET scans were interpreted as active vasculitis in 28 (55%) of 51 patients. FDG-PET activity at enrollment was not associated with clinical symptoms, acute phase reactants, or risk of flare. Younger age (70 vs 76 years; P = 0.03) and female sex (89% vs 48%, P < 0.01) were significantly associated with increased FDG-PET activity. There were no differences in prior glucocorticoid dose (median 780 mg) or duration (median 23 days) between patients with baseline active versus inactive FDG-PET scans. FDG-PET scans were active in 17 of 21 (81%) patients during clinical flare and in 14 of 20 (70%) patients at week 52. Subsets of patients had persistently active (n = 21) or inactive (n = 9) PET scans at all time points, independent of clinical assessment. CONCLUSION:Vascular FDG-PET activity may be discordant with clinical assessment, particularly in subsets of patients with GCA. Imaging-based outcome measures should remain exploratory in future therapeutic trials.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related chronic inflammatory conditions. Glucocorticoids remain the cornerstone of treatment for both conditions, as they rapidly control inflammation and also reduce the risk of ischaemic complications in GCA. However, glucocorticoid therapy is often prolonged and associated with substantial treatment-related morbidity. In addition, many patients experience relapses during glucocorticoid maintenance therapy and can accrue vascular damage. Advances in understanding the immunopathology of GCA and PMR have led to the development of targeted therapies, particularly agents inhibiting the IL-6 pathway and, more recently, Janus kinase (JAK) signalling. IL-6 receptor inhibitors reduce the risk of disease relapse and allow for reduction in glucocorticoid use in both GCA and PMR, and JAK inhibition enables glucocorticoid sparing and lowers the risk of relapse in GCA. Optimal management of GCA and PMR requires close monitoring, careful assessment of disease activity and treatment-related toxicity, as well as individualized therapeutic strategies. Ongoing research continues to refine treatment algorithms and could help to define therapeutic targets across GCA and PMR. Emerging therapeutic options and evolving treatment algorithms reflect the dynamic and patient-centred nature of advancements in GCA and PMR management.

OBJECTIVES:Giant cell arteritis (GCA) is a clinically heterogeneous disease, which complicates both diagnosis and management. This study aimed to identify genetic risk factors associated with GCA clinical manifestations and evaluate their utility for defining clinical phenotypes. METHODS:Genome-wide genotype data from 3498 patients with GCA and 15,550 controls were analysed to investigate the genetic architecture of GCA manifestations. Logistic regression was used to compare patients with and without each manifestation, as well as each subgroup of patients vs controls. Gene annotation was conducted based on functional information using Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA GWAS). Latent class analysis (LCA) was applied to evaluate the ability of associated variants to classify patients with GCA into genetic subgroups. RESULTS:We identified 7 human leukocyte antigen (HLA) variants specifically associated with different clinical features. Furthermore, 7 non-HLA associations across 6 clinical manifestations were found. Gene prioritisation highlighted biologically relevant candidate genes for GCA pathogenesis, including IL17A (limb claudication) and IL22RA1 (jaw claudication), both involved in the Th17 pathway, and ATP2A2 (extracranial form), encoding a transporter that promotes aortic aneurysms. Notably, LCA grouped GCA clinical predisposition into 4 classes capturing cranial-predominant, mixed, extracranial, and ischaemic/occlusive patterns, the latter representing a high-risk subgroup for severe ischaemic and ocular complications. CONCLUSIONS:This first genome-wide association study stratified by GCA-specific manifestations deepens our understanding of the genetic basis underlying GCA clinical heterogeneity. Our findings highlight HLA and non-HLA contributors to specific disease phenotypes and support the potential of genetic profiling to guide early diagnosis and personalised management in GCA.

OBJECTIVES:Guselkumab, a monoclonal antibody, selectively targets the p19 subunit of interleukin-23. This randomised, double-blind, placebo-controlled, phase 2 study evaluated guselkumab vs placebo for the treatment of giant cell arteritis (GCA). METHODS:Patients ≥50 years of age with new-onset or relapsing GCA were randomised 2:1 to guselkumab or placebo. Both arms received background glucocorticoid (GC) therapy, with a protocol-defined taper through week 26. The primary endpoint was the proportion of patients achieving GC-free remission at week 28. RESULTS:Thirty-five patients were randomised to receive guselkumab and 18 to receive placebo. All patients were White, 70% were female, and the mean age was 71.5 years; 60% had new-onset and 40% had relapsing GCA. At week 28, 40% (14/35) and 33% (6/18) of patients in the guselkumab and placebo groups, respectively, achieved GC-free remission (P = .64), whereas 31% (11/35) and 39% (7/18) had experienced a GCA flare or discontinued due to worsening GCA. Median time to first GCA flare through week 28 was not estimable (NE) in the guselkumab group (90% CI: 27.7-NE) and 29.7 weeks (90% CI: 20.1-NE) in the placebo group (P = .64). Through week 60, 97% (34/35) and 94% (17/18) of patients in the guselkumab and placebo groups, respectively, had adverse events (AEs); the most common AEs, aside from worsening of GCA (49% and 56%, respectively), were COVID-19 infection (23% and 28%) and headache (17% and 39%). CONCLUSIONS:The study's primary endpoint (GC-free remission) was not met; results do not support the use of guselkumab in the treatment of GCA.

Objectives This study aimed to update the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of polymyalgia rheumatica (PMR), giant cell arteritis (GCA), and Takayasu arteritis (TAK). Methods Following EULAR standard operating procedures, systematic literature reviews identified data published since the previous versions for PMR (2015) and for GCA/TAK (2018). An international task force discussed the evidence, and following a structured voting process, created overarching principles, recommendations, and quality indicators. Results The task force agreed on 4 overarching principles, 12 recommendations, and 2 quality indicators. All patients with suspected PMR, GCA, or TAK should be referred for specialist assessment and those with suspected GCA within 24 hours. In patients with a strong clinical suspicion of GCA, treatment with glucocorticoids (GCs) should be commenced without delay, while waiting for the results of confirmatory investigations. For most patients with suspected PMR or TAK, treatment with GC can be delayed until the diagnosis is confirmed. For induction of remission, GC should be initiated at a dose of 15 to 25 mg/day prednisone-equivalent for PMR and 40 to 60 mg for GCA or TAK. Guidance on GC tapering is provided. Adjunctive therapy is recommended for selected patients with PMR or GCA using either interleukin (IL)-6 receptor inhibitors for PMR and GCA or upadacitinib for GCA. Methotrexate may be an alternative. GC-sparing agents should be given in combination with GC to all patients with TAK. All overarching principles and recommendations met with high levels of agreement. Conclusions Updated guidance on management of PMR and large vessel vasculitis is provided in a single set of practical recommendations and algorithms.

IgA vasculitis (IgAV) is an immune complex-mediated small-vessel vasculitis that typically affects the skin, gastrointestinal tract, kidneys and joints. Childhood-onset IgAV is a common disease and usually follows a self-limiting course, whereas adult-onset IgAV is considerably less frequent and is associated with a poorer prognosis. The diagnosis, assessment and management of adult-onset IgAV remain challenging owing to the absence of validated diagnostic criteria for adults and lack of IgAV-specific standardized disease activity scores. Short-term outcomes are mainly determined by gastrointestinal complications, whereas kidney involvement and the risk of progression to chronic kidney disease are the major determinants of long-term prognosis. The treatment of adult-onset IgAV is limited by the paucity of high-quality clinical trials and standardized therapeutic approaches. Here, we present evidence-based, multidisciplinary guidelines for the diagnosis and management of adult-onset IgAV that reflect advances in understanding of pathogenesis, differential diagnoses and treatment over the past two decades. Developed by a panel of leading European experts on the basis of systematic literature review and expert opinion, these guidelines comprise 14 recommendation statements and overarching principles that provide a structured and pragmatic clinical framework for the diagnosis, treatment and follow-up of adult-onset IgAV.

Objectives Both temporal artery biopsy (TAB) and imaging are widely used to support the diagnosis of giant cell arteritis (GCA). The objective of this study was to compare the use of TAB and imaging. Methods This article was based on a debate presented at the 21st Vasculitis Meeting, discussing the advantages and disadvantages of using TAB with histology vs imaging for the diagnosis of suspected GCA. Results TAB is the diagnostic procedure with the highest specificity. Its sensitivity may be improved by removing an appropriate artery length, practice, examining multiple sections at various levels, and by recognizing incomplete histological findings (which may lead to a more definitive diagnosis by further sectioning or imaging or be related to other inflammatory diseases). TAB may provide histopathological clues useful for diagnosing GCA mimics that may produce similar imaging abnormalities. TAB is a useful research resource, and our current understanding of GCA physiopathology mostly relies on tissue immunopathology studies. Conclusion A suspected diagnosis of GCA should be supported by an objective test. TAB is the procedure with the highest specificity, and its sensitivity may be improved by training. Histopathologic examination provides data for an alternative diagnosis, when diseases other than GCA involve the temporal artery. Imaging is essential for the assessment of large-vessel involvement and allows follow-up studies.

Objectives To prospectively evaluate the impact and the rapidity of the effect of mepolizumab on the ANCA-associated vasculitis patient-reported outcomes (AAV-PRO) questionnaire and patient global assessment (PtGA) in an international, multicentre cohort of patients with eosinophilic granulomatosis with polyangiitis (EGPA). Methods Patients with active EGPA initiating treatment with mepolizumab were included. PtGA and the AAV-PRO score were assessed at baseline and after 7, 14, 30, 90 and 180 days. Predictors of response of the AAV-PRO questionnaire were investigated. Results Seventy patients were included: female 54.3%, median age 56 years (48—65), 63 (90%) with a relapsing/refractory course. PtGA showed a statistically significant decrease within 7 days. At 14 days, all the AAV-PRO domains, except treatment side effects, showed a statistically significant decline. The improvement at 6 months was greatest in organ-specific symptoms (ratio 0.53), physical function (ratio 0.57), and PtGA (ratio 0.58). PtGA and higher disease activity positively correlated with the AAV-PRO scores throughout the study. Female patients reported a greater burden in terms of systemic symptoms, treatment side effects, social and emotional impact, and concerns about the future. Conversely, age, educational level, damage accrual, mepolizumab dose and ANCA status had no effect on the AAV-PRO scores. Conclusions Mepolizumab was associated with a quick and remarkable improvement of health-related quality of life in patients with EGPA. These findings highlight its early and sustained benefits beyond disease control and support the integration of the AAV-PRO questionnaire into routine clinical practice.

OBJECTIVES:Blocking interleukin (IL)-6-receptor with tocilizumab has been a major advance in the treatment of giant-cell arteritis (GCA), supporting a crucial role of IL-6 receptor signalling. However, nearly half of the patients are not able to maintain glucocorticoid- free remission with tocilizumab. The impact of tocilizumab on vascular lesions of GCA is largely unknown since conflicting results have been obtained by imaging. The expression and functional role of IL-6-receptor in GCA immunopathology has not been previously investigated. This study aimed to investigate expression of IL-6 receptor in GCA and control arteries and to assess the impact of tocilizumab on ex vivo-cultured temporal arteries and aortic tissue from patients with GCA. METHODS:This study used a hypothesis-driven, candidate molecule transcriptomic approach using ex vivo temporal artery and aortic tissue culture, quantitative real-time polymerase chain reaction, immunofluorescence, Western Blot, immunoassay, adhesion, and chemotaxis assays. RESULTS:IL-6 receptor protein expressed intensively in GCA compared with that in control arteries. Tocilizumab decreased expression/phosphorylation of STAT3 and reduced expression of STAT3-dependent molecules including suppressor of cytokine signalling 3, CCL-2, and ICAM-1 in cultured GCA-involved arteries and patients' peripheral blood mononuclear cells (PBMCs). A similar trend was observed in aortic tissue. Consistently, tocilizumab reduced PBMC adhesiveness to vascular smooth muscle cells and human umbilical vein endothelial cells and chemotaxis towards supernatants of tocilizumab-treated GCA arteries. In some specimens, tocilizumab increased STAT1 phosphorylation and expression of STAT1-dependent chemokines including CXCL9 and CXCL10. CONCLUSIONS:Tocilizumab has a significant impact on vascular lesions by reducing, but not abrogating, key molecules involved in PBMC recruitment. About half of the patients may activate alternative inflammatory pathways in their lesions as a potential escape mechanism to tocilizumab that deserves further investigation.

OBJECTIVES:This study seeks to create consensus-based definitions of signs and symptoms of giant cell arteritis (GCA) for use by health care professionals, primarily in research settings. METHODS:Core definitions of signs and symptoms of GCA were extracted from 11 randomised controlled trials of GCA previously reviewed in a systematic literature review conducted in the context of the development of response criteria for GCA. This information was supplemented by definitions from other sources, such as rheumatology textbooks. A 2-round Delphi was performed within an international task force (32 members from 11 countries). The first round aimed to obtain consensus on the descriptive terms defining each sign or symptom, and round 2 rated the importance of these terms. Based on the Delphi study method, preliminary definitions were developed. In 4 online meetings, results of the Delphi were reviewed, and a consensus was achieved on final definitions. RESULTS:Twenty-nine signs and symptoms of GCA were reviewed. Six signs or symptoms of GCA had previously been defined in the literature. A high level of agreement was reached on the definition of 23 signs and symptoms with the following 12 considered characteristic of GCA: headache, temporal artery abnormalities, scalp tenderness, scalp necrosis, jaw claudication, tongue claudication, tongue necrosis, amaurosis fugax, permanent vision loss, fever, limb claudication, and blood pressure inequality. CONCLUSIONS:A glossary of definitions for 23 signs and symptoms of GCA was developed through a consensus process involving international experts.