Objectives:To externally validate the PMR impact scale (PMR-IS). Methods:We conducted a prospective cohort study at the University Hospitals Leuven, Leuven, Belgium. Recently diagnosed PMR patients were included between July 2022 and December 2023 and followed until 1 year after diagnosis. All patients completed the PMR-IS, HAQ Disability Index, 36-item Short Form and a visual analogue scale for pain at every visit. Internal consistency, floor and ceiling effects, construct validity, responsiveness and discriminatory power for detecting relapse on the PMR-IS were assessed. Results:Fifty-five PMR patients (mean age 71 years, 47% female) were included, who had a total of 246 visits. Internal consistency, construct validity and responsiveness met the quality criteria for the symptoms, function and emotional and psychological well-being subdomains. The internal consistency of the glucocorticoid side effects subdomain was insufficient and only one of the three hypotheses for construct validity were met. The function and emotional and psychological well-being subdomains showed a floor effect, while no ceiling effect was observed. The symptoms, function and emotional and psychological well-being subdomains had a good discriminatory power for detecting relapse [area under the curve (AUC) 0.89, 0.86 and 0.72, respectively], but the PMR activity score performed better (AUC 0.94, P < 0.05 for all subdomains). Conclusion:This study validates the good measurement properties of the symptoms, function and emotional and psychological well-being subdomains of the PMR-IS. In contrast, the glucocorticoid side effects subdomain did not show adequate internal consistency and construct validity, necessitating further validation and possibly refinement of its items prior to application in clinical trials or daily practice.

To evaluate the diagnostic accuracy of PET/CT, cranial MRI, ultrasound and temporal artery biopsy (TAB) in patients with suspected giant cell arteritis (GCA) in a direct comparison. Consecutive patients with a suspicion of GCA and at least 2 diagnostic tests ≤ 7 days after initiation of glucocorticoids between June 2021 and June 2024, were included retrospectively. The gold standard for the diagnosis of GCA was the judgment of experienced clinicians after a follow-up of ≥ 6 months. Examinations were compared within subgroups undergoing the same tests. Sixty-one GCA patients and 50 patients with an alternative diagnosis were included. Combined cranial and large vessel PET/CT had the highest sensitivity (89

OBJECTIVE:To validate the polymyalgia rheumatica-activity score (PMR-AS). METHODS:Prospective cohort study at the University Hospitals Leuven (Belgium) between July 2022 and December 2023. We created a new alternative PMR-AS in which ability to elevate the upper limbs (EUL) was replaced by visual analogue scale (VAS) of functionality and both the severity and the duration of stiffness were evaluated. The discriminatory capacity for detecting active disease of the PMR-AS, the change in PMR-AS and several alternative scores were assessed using area under the receiver operating characteristic curves (AUC) and compared using Delong's tests. GEE-logistic prediction models were used to correct for repeated measures. RESULTS:We included 133 PMR patients (419 visits). PMR-AS had a good discriminatory power with an AUC of 0.938 and an optimal cut-off point of 11.0 with corresponding sensitivity of 87 % and specificity of 87 %. The change in PMR-AS (AUC 0.862), clinical-PMR-AS (AUC 0.928) and imputed-PMR-AS (AUC 0.928) significantly performed worse in detecting active disease (all p≤0.010). The ESR-PMR-AS also tended to have a lower discriminatory capacity (AUC 0.932, p=0.050). Our alternative PMR-AS had a higher AUC (AUC 0.948, p=0.010) with an optimal cut-off point of 13.5 and corresponding sensitivity of 87 % and specificity of 88 %. CONCLUSION:PMR-AS had a good discriminatory capacity for detecting active disease, but the alternative PMR-AS performed slightly better. Alternative activity scores which do not require the use of CRP performed slightly worse but can be used in case of treatment with glucocorticoid-sparing agents affecting the CRP level.

BACKGROUND:Giant-cell arteritis is a systemic vasculitis with limited treatment options. The efficacy and safety of upadacitinib - a selective Janus kinase (JAK) inhibitor that blocks the signaling of several cytokines, including interleukin-6 and interferon-γ - are unknown in patients with giant-cell arteritis. METHODS:We randomly assigned patients with new-onset or relapsing giant-cell arteritis, in a 2:1:1 ratio, to receive upadacitinib at a dose of 15 mg or 7.5 mg orally once daily plus a 26-week glucocorticoid taper or placebo plus a 52-week glucocorticoid taper. The primary end point was sustained remission at week 52, defined by the absence of signs or symptoms of giant-cell arteritis from week 12 through week 52 and adherence to the protocol-specified glucocorticoid taper. RESULTS:A total of 209 patients received upadacitinib at a dose of 15 mg, 107 received upadacitinib at a dose of 7.5 mg, and 112 received placebo; 70% of the patients had new-onset giant-cell arteritis. Upadacitinib at a dose of 15 mg showed superiority over placebo with respect to the primary end point (46.4% [95% confidence interval {CI}, 39.6 to 53.2] vs. 29.0% [95% CI, 20.6 to 37.5]; P = 0.002). Upadacitinib at a dose of 15 mg was superior to placebo in the analysis of the hierarchically prespecified and multiplicity-controlled key secondary end points of sustained complete remission, time to a disease flare, cumulative glucocorticoid exposure, and patient-reported outcomes. Upadacitinib at a dose of 7.5 mg was not superior to placebo with respect to the primary end point (41.1% [95% CI, 31.8 to 50.4]). Safety outcomes during the treatment period of 52 weeks were similar in the upadacitinib and placebo groups. Although cardiovascular risk is a potential concern with a JAK inhibitor, no major adverse cardiovascular events occurred in the upadacitinib groups. CONCLUSIONS:In patients with giant-cell arteritis, upadacitinib at a dose of 15 mg - but not 7.5 mg - with a 26-week glucocorticoid taper showed efficacy superior to that of placebo with a 52-week glucocorticoid taper. (Funded by AbbVie; SELECT-GCA ClinicalTrials.gov number, NCT03725202.).

The breakout session “Imaging in Disease Assessment” featured six abstracts on imaging advancements for vasculitis. Disease extent on cranial MRI and its association with visual complications in giant cell arteritis (GCA) was evaluated, introducing the Propensity for Enhancement for GCA (P EG) score to assess inflammation. Predictors of remission and relapse in chronic periaortitis were analyzed, suggesting the potential for tailored treatment approaches. A novel radiomic model using CT chest scans accurately predicted relapses in ANCA-associated vasculitis. FDG-PET for monitoring GCA in patients on tocilizumab demonstrated limited predictive value. Comparative assessments of Takayasu arteritis using the Takayasu Arteritis Disease Activity Index (TAIDAI) highlighted the need for standardized evaluations. Finally, a protocolized ultrasonography pathway for diagnosing large vessel vasculitis showed promising results, suggesting a combined ultrasound and second test approach, guided by CRP levels, as a gold standard. The session emphasized integrating imaging biomarkers with clinical assessments to improve disease management.

OBJECTIVES:To evaluate differences in presentation and outcome of GCA patients with and without large vessel vasculitis (LVV) and according to the extent and severity of LVV. METHODS:Consecutive patients diagnosed with GCA between 2003 and 2020 who have had FDG PET imaging at diagnosis ≤3 days after initiation of glucocorticoids (GC) and followed for ≥12 months at the University Hospitals Leuven (Belgium) were included retrospectively. PET scans were visually scored (0-3) in seven vascular areas and a total vascular score (TVS) was calculated. LVV was defined as FDG uptake ≥2 in any large vessel. RESULTS:We included 238 GCA patients, of which 169 (71%) had LVV. LVV patients were younger (69 vs 74 years, P < 0.001) and more frequently female (72% vs 49%, P = 0.001). In patients without PMR symptoms, the presence of LVV was associated with relapse (aOR 3.05 [95% CI 1.32-7.43], P = 0.011) and with a lower probability of stopping GC (aHR 0.59 [95% CI 0.37-0.94], P = 0.025). However, in those with PMR symptoms, there was no difference in relapse risk (aOR 1.20 [95% CI 0.53-2.66], P = 0.657) and in the probability of stopping GC (aHR 1.25 [95% CI 0.75-2.09], P = 0.394) between patients with and without LVV. A higher TVS was associated with an increased risk of relapse (aOR 1.09 [95% CI 1.04-1.15], P = 0.001) in patients without PMR symptoms, but not in those with PMR symptoms (aOR 1.01 [95% CI 0.96-1.07], P = 0.693). CONCLUSION:LVV is a risk factor for relapse in GCA patients without PMR symptoms with a higher relapse risk in those with higher TVS.

In this article, the author explains the relationship between GCA and PMR, based on historical studies, his own experience with a large group of patients and recent publications. Searching for occult vasculitis in patients with pure PMR is recommended and the author explains why PET is well suited for this purpose.

OBJECTIVES:Two recent meta-analyses reported subclinical vasculitis in 22-23% of patients with PMR. We aimed to evaluate the prevalence, characteristics, and outcome of subclinical vasculitis among our PMR patients. METHODS:Consecutive patients with GCA/PMR spectrum disease with isolated PMR symptoms who underwent FDG PET imaging between 2003 and 2020 and who were followed for ≥6 months, were included retrospectively. Vasculitis was defined as FDG uptake ≥grade 2 in any vessel. RESULTS:We included 337 patients, of whom 31 (9%) with subclinical vasculitis. Among those with subclinical vasculitis, 21 (58%) had isolated large vessel vasculitis, 3 (10%) had isolated cranial vasculitis and 7 (23%) had both cranial and large vessel vasculitis. The glucocorticoid (GC) starting dose and GC doses during follow-up were higher in those with subclinical vasculitis until 12 months after diagnosis (P < 0.001). There was no difference in the duration of GC treatment (25 vs 20 months, P = 0.187). Cox proportional hazard regression analyses showed no difference in the proportion of patients able to stop GC (HR 0.78 [95% CI 0.49-1.25], P = 0.303) and in the proportion of patients with relapse (HR 0.82 [95%CI 0.50-1.36], P = 0.441). CONCLUSION:Only 9% of our PMR patients had subclinical vasculitis with a predilection for large vessel vasculitis. There were no differences in relapse rate and duration of GC treatment, however, those with subclinical vasculitis received higher GC doses until 12 months after diagnosis. Prospective interventional trials are needed to evaluate the outcome of PMR patients with and without subclinical vasculitis treated with a similar GC protocol.

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.

Objectives To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV). Methods A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes. Results Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation. Conclusions The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV.

AbstractBackgroundVEXAS ‘Vacuoles, E1 Enzyme, X‐linked, Autoinflammatory, Somatic syndrome’ is a rare autoinflammatory syndrome, first described in October 2020 by Beck et al. It is caused by somatic mutations in the UBA1 gene, coding for the E1 enzyme, responsible for ubiquitination. It manifests in adulthood, mainly in men, with constitutional symptoms, haematological abnormalities and often skin lesions with neutrophilic dermatoses most frequently reported. Since skin lesions are a frequent and early manifestation, recognising these may prove very useful for diagnosis.ObjectivesTo focus on the dermatological manifestations of VEXAS and their histopathological correlate.MethodsWe retrospectively collected data and revised skin biopsies of VEXAS patients diagnosed in our tertiary care centre, and compared those with the literature.ResultsWe identified nine men between 62 and 84 years old. The most frequently encountered UBA1 mutation was p.Met41Thr. Skin manifestations occurred in all patients; mostly as erythematous to purpuric papules/plaques, often with annular pattern. Histopathological, early VEXAS lesions showed a gradient in infiltrate with neutrophils being concentrated in the superficial interstitium and lymphocytes situated deeper around the blood vessels. Later in the disease course, the pattern became more variable and less specific with more nuclear debris, histiocytes, neutrophils and ulceration. Haematological and constitutional manifestations were present in all patients, followed by musculoskeletal (88.8%), eye (77.7%) and cardiovascular manifestations (66.6%). Polychondritis was present in 6/9 (66.6%) patients, as were respiratory symptoms, though only 33.3% had proven lung disease. The mortality rate was 22% 10 months after diagnosis.ConclusionsThis is the first cohort which describes in detail VEXAS skin manifestations with revision of all available skin biopsies, which led to the conclusion that early histopathological abnormalities in VEXAS syndrome may be easy to recognise, while the histopathological image becomes less specific over time and mimics other diseases as VEXAS progresses.

Background Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. Methods Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. Results Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4–5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. Conclusions In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.

Objectives: To evaluate differences in presentation and outcome of giant cell arteritis (GCA) patients with and without polymyalgia rheumatica (PMR) symptoms. Methods: Consecutive patients diagnosed with GCA between 2000 and 2020 and followed for >= 12 months at the University Hospitals Leuven (Belgium), were included retrospectively. Results: We included 398 GCA patients, of which 181 (45%) with PMR symptoms. Patients with PMR symptoms had a longer symptom duration (11 vs 6 weeks, p < 0.001). They less frequently reported fever (19% vs 28%, p = 0.030) and fatigue (52% vs 64%, p = 0.015) and tended to have less permanent vision loss (12% vs 19%, p = 0.052). There was no difference in the cumulative oral GC dose at 2 years (4.4 vs 4.3 g methylprednisolone, p = 0.571). However, those with PMR symptoms were treated with higher GC doses during subsequent follow-up (p < 0.05 from 38 months after diagnosis) and had a lower probability of stopping GC (62% vs 71%, HR 0.74 [95%CI 0.58-0.94], p = 0.018) with a longer median duration of GC treatment (29 vs 23 months, p = 0.021). In addition, presence of PMR symptoms was associated with an increased risk of relapse (64% vs 51%, HR 1.38 [95%CI 1.06-1.79], p = 0.017) with a higher number of relapses (1.47 [95%CI 1.30-1.65] vs 1.16 relapses [95%CI 1.02-1.31], p = 0.007). Patients with PMR symptoms less frequently developed thoracic aortic aneurysms during follow-up (3% vs 11%, p = 0.005). Conclusion: GCA patients with PMR symptoms had more recalcitrant disease with a higher risk of relapse and longer duration of GC treatment with need for higher GC doses.

BackgroundA positive PET scan at diagnosis was associated with a greater yearly increase in ascending and descending aortic diameter and thoracic aortic volume in patients with giant cell arteritis (GCA). Radiologic and histopathologic vascular abnormalities persist in a subset of treated patients despite clinical remission. The aim of this study was to evaluate the association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms.MethodsWe recently performed a prospective cohort study of 106 GCA patients, who underwent FDG PET and CT imaging at diagnosis and CT imaging yearly for a maximum of 10 years. In this post hoc analysis, GCA patients who also have had FDG PET imaging during follow-up were included. PET scans were visually scored (0–3) at 7 vascular areas. PET scans were considered positive in case of FDG uptake ≥grade 2 in any large vessel.ResultsEighty-eight repeat PET scans were performed in 52 out of 106 GCA patients, who were included in the original prospective cohort. Fifty-five (63%) PET scans were done at the time of a relapse and 33 (38%) were done while in remission. Nine out of ten patients with an incident thoracic aortic aneurysm had both a positive PET scan at diagnosis and during follow-up.ConclusionIn addition to the intensity and extent of the initial vascular inflammation, ongoing aortic inflammation may contribute to the development of thoracic aortic aneurysms in GCA. However, this hypothesis should be confirmed in a large prospective trial with repeat PET scans at predefined time points during follow-up.

Background: About half of patients with giant cell arteritis (GCA) experience disease relapse. However, the relationship between symptoms at diagnosis and at time of relapse remains unknown. Objectives: To compare the symptoms at diagnosis with those at time of first relapse in GCA patients. Methods: Patients with a diagnosis of GCA between 2000 and 2020 who were followed for ≥12 months at the University Hospitals Leuven, were included retrospectively. Relapse was defined as recurrence of clinical symptoms compatible with polymyalgia rheumatica (PMR) or GCA and/or increase of inflammatory markers requiring escalation of treatment. Symptoms were categorized as constitutional, PMR, cranial, or limb claudication. As patients could present or relapse with symptoms in >1 category, cumulative percentages add up to >100%. Results: We included 398 GCA patients (mean age 72 years, 64% females). Median duration of follow-up was 42 months (IQR 24-83). Relapse occurred in 224 patients (56%). The median time since diagnosis until first relapse was 13 months (IQR 9-17) with a median daily dose of methylprednisolone of 1 mg (IQR 0-4). Figure 1 shows the distribution of symptoms at diagnosis and at time of first relapse. At diagnosis, 302 (76%) patients had constitutional symptoms, 296 (74%) cranial symptoms, 181 (45%) PMR symptoms and 8 (2%) limb claudication. At first relapse, 79 (35%) patients reported constitutional symptoms, 77 (34%) cranial symptoms, 136 (61%) PMR symptoms and 3 (1%) limb claudication. The symptoms at first relapse divided according to symptoms at diagnosis are presented in Table 1. Despite having no cranial or PMR symptoms at diagnosis, 21/33 (64%) patients with isolated constitutional symptoms and/or raised inflammatory markers had PMR symptoms and 6/33 (18%) had cranial symptoms at time of first relapse. Of the 73 patients with isolated cranial symptoms at diagnosis with at least one relapse, only 43 (59%) had cranial symptoms at time of first relapse, while 26 (36%) had PMR symptoms for the first time. Conclusion: PMR was the most frequent symptom at time of first relapse in GCA patients, whereas cranial and constitutional symptoms were more frequently reported at diagnosis. Even in patients without PMR symptoms at diagnosis, PMR is a common symptom at time of first relapse. Our hypothesis is that cranial and constitutional symptoms more frequently occur in case of high disease activity, whereas PMR is an early, less severe phenotype of the GCA-PMR spectrum, which first reappears in case of increased disease activity. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Lien Moreel Roche, Albrecht Betrains: None declared, Steven Vanderschueren: None declared, Daniel Blockmans Roche, GSK, Eli Lily, Roche.Figure 1Distribution of symptoms at diagnosis and at time of first relapse Table 1The symptoms at time of first relapse divided according to symptoms at diagnosis (Table 1 linked to abstract AB1291)Total°(n=398)Isolated cranial symptoms(n=156)Cranial and PMR symptoms(n=138)Isolated constitutional symptoms and/or raised inflammatory markers(n=57)Isolated PMR symptoms(n=39)Limb claudication* (n=8)Relapse, n(%)224 (56%)73 (47%)90 (65%)33 (58%)21 (54%)7 (88%)Time to first relapse, months, median (IQR)13 (9-17)11 (7-16)13 (9-17)16 (10-17)14 (11-18)16 (9-17)Dose of methylprednisolone, mg/day, median (IQR)1 (0-4)22 (0-4)21 (0-3)0 (0-2)1 (0-4)2 (0-3)Symptoms at first relapse, n(%)○ PMR136/224 (61%)26/73 (36%)68/90 (76%)21/33 (64%)17/21 (81%)4/7 (57%)○ Cranial symptoms77/224 (34%)43/73 (59%)27/90 (30%)6/33 (18%)1/21 (5%)0/7 (0%)○ Constitutional symptoms79/224 (35%)27/73 (37%)29/90 (32%)18/33 (55%)4/21 (19%)1/7 (14%)○ Limb claudication3/224 (1%)1/73 (1%)0/90 (0%)0/33 (0%)0/21 (0%)2/7 (29%)Abbreviations: IQR, interquartile range; PMR, polymyalgia rheumaticaNumber of missing values are reported in superscript.° All patients could have constitutional symptoms at diagnosis.* Among the patients with limb claudication, 4 patients also reported PMR symptoms and 2 cranial symptoms

Objective To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR).Methods A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated.Results Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care.Conclusions These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR.

Introduction Les corticoïdes (GC) restent la principale option thérapeutique de l’artérite à cellules géantes (ACG). L’upadacitinib (UPA), un inhibiteur oral et sélectif de JAK, approuvé pour traiter plusieurs maladies inflammatoires, a le potentiel de traiter l’ACG. Patients et méthodes SELECT-GCA est une étude randomisée de phase III, en double aveugle contrôlée vs PBO dont l’objectif est d’évaluer l’efficacité et la tolérance d’UPA en association avec une diminution progressive des GC, chez des patients ayant une ACG. Sont rapportés ici les résultats de l’analyse principale à 52 semaines (S). Les patients ont reçu l’UPA 7,5mg (UPA7,5) ou 15mg (UPA15), avec une diminution des GC sur 26S ou un PBO avec une diminution des GC sur 52S. Les patients éligibles avaient≥50 ans, un diagnostic ou une rechute d’ACG, avaient été traités par≥40mg/j de prednisone ou équivalent avant l’inclusion (incl), et étaient traités par prednisone≥20mg/j à l’incl. Les patients traités antérieurement par inhibiteurs de JAK, ayant eu une réponse inadéquate ou traités par des anti-IL-6 au cours des 4S précédant l’incl ou ayant une utilisation chronique de GC systémiques étaient exclus. Le critère principal était la rémission maintenue, définie par l’absence de signes ou symptômes d’ACG entre S12 et S52 et le respect du schéma de réduction des GC prévu au protocole. Les critères secondaires incluaient la rémission complète maintenue (rémission maintenue avec normalisation de la VS et de la CRP), des critères liés aux poussées de la maladie, et l’exposition cumulée aux GC. Les événements indésirables (EI) ont été documentés durant les 52S. Résultats Au total, 428 patients ont été randomisés et traités (PBO : n=112 ; UPA7,5 : n=107 ; UPA15 : n=209). Les caractéristiques à l’incl étaient comparables entre les groupes de traitement. Le critère principal de rémission maintenue à S52 a été atteint avec l’UPA15 vs le PBO (46 % vs 29 %, p=0,0019) et 9/11 critères secondaires contrôlés pour la multiplicité des tests ont été atteints avec l’UPA15, y compris la rémission complète maintenue de S12 à S52 (37 % vs 16 %, p<0,0001). Une diminution du risque de poussées a été observée avec l’UPA15 par rapport au PBO au cours des 52S (Fig. 1). L’exposition médiane cumulée aux GC sur les 52S a été significativement plus faible avec l’UPA15 vs le PBO (1615mg vs 2882mg, p<0,0001). Pour la plupart des critères, une amélioration numériquement supérieure à celle du PBO a été observée avec l’UPA7,5. Les résultats de tolérance étaient généralement similaires dans les groupes UPA et PBO (Tableau 1), avec des taux plus élevés d’infections graves et de MACE rapportés dans le groupe PBO et aucun MACE rapporté dans les groupes UPA. Les taux de zona, lymphopénie, anémie et cancer cutané non-mélanome (CCNM) étaient numériquement plus élevés avec UPA15 vs PBO. Les taux d’évènements thromboemboliques étaient comparables dans tous les groupes de traitement. Les taux d’EI graves et de cancers (hors CCNM) étaient similaires entre UPA15 et le PBO. Quatre décès ont été rapportés : deux dans le groupe PBO et deux dans le groupe UPA15 (un attribuable au COVID-19 et un de cause inexpliquée). Conclusion L’UPA15 a démontré une efficacité supérieure et une utilisation réduite des GC par rapport au PBO. Aucun nouveau signal de tolérance n’a été identifié avec UPA par rapport au profil connu [1]. L’UPA15 a présenté un rapport bénéfice/risque favorable et représente un nouveau traitement ciblé potentiel pour les patients atteints d’ACG.