[This corrects the article DOI: 10.1016/j.ero.2025.11.014.].

OBJECTIVES:Polymyalgia rheumatica (PMR) is the second most frequent inflammatory rheumatic disease in older adults, after rheumatoid arthritis. Recommendations for the management of PMR, developed by the German, Austrian and Swiss societies of rheumatology and other organizations were published in 2018. METHODS:These recommendations are now updated based on a systematic literature search that covered the evidence published between July 2016 and January 2024 on therapeutic interventions and prognostic factors for PMR. The search string followed that used in the original recommendations, with an extension for targeted synthetic disease-modifying antirheumatic drugs (DMARDs). Based on evidence and expert opinions, the task force (12 physicians, two healthcare professionals and two patients from three countries) developed a set of four overarching principles and seven specific recommendations. RESULTS:The current update reiterates previous guideline recommendations for glucocorticoids (15-25 mg prednisone equivalents per day) as initial treatment for PMR once diagnosis has been confirmed, with subsequent tapering over 4-12 months (depending on whether a glucocorticoid sparing agent is used), with monitoring of disease activity and treatment-related adverse effects. Interleukin-6 receptor blocking agents should be considered in addition to glucocorticoids in patients with relapsing disease and can be considered in patients with new-onset PMR at high risk for glucocorticoid-related adverse events. Methotrexate or rituximab may be alternatives. Older and frail patients should also be offered an individualized exercise program. CONCLUSION:These updated recommendations should serve as an aid to evidence-based decisions ensuring high-quality care for all patients with PMR.

Abstract:Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the predominant types of large-vessel vasculitis, sharing IL-6-mediated immunopathology but differing in age profile and clinical phenotype. Glucocorticoids (GC) remain standard for induction therapy, although relapse rates and treatment-associated toxicity on GC monotherapy are high. Therefore, current guidelines support early tapering and the use of GC-sparing agents in relapsing or high-risk patients. Tocilizumab is now established as standard therapy in GCA, while methotrexate remains an alternative option. Recently, the janus kinase (JAK) inhibitor upadacitinib has gained regulatory approval for GCA, supported by results of a phase 3 trial. In TAK, conventional immunosuppressants are used in new-onset disease, while TNF-alpha or IL-6-blockade can be considered in relapsing or refractory disease. Optimal duration of treatment is not yet well defined.

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.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of frequently relapsing systemic autoimmune disorders characterized by vasculitis-related organ damage and multiple comorbidities related to chronic inflammation. Advances in immunosuppression-based therapies for AAV have considerably improved remission rates, reduced the risk of relapse, and improved survival in patients with AAV. However, mortality remains high compared with the general population and the benefits of treatment are often offset by treatment-related comorbidities, organ damage and adverse effects, particularly infections. The aim of this review is to investigate the key contributors to disease burden in patients with AAV and to describe strategies for improving health-related quality of life.

Objectives This study aimed to systematically review the literature on polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV) referral and diagnosis to inform the 2025 European Alliance of Associations for Rheumatology recommendations on the management of PMR and primary LVV. Methods A systematic literature review focused on referral and diagnosis of PMR, giant cell arteritis (GCA), and Takayasu arteritis (TAK) was conducted across MEDLINE, Embase, and Cochrane for randomised trials, observational studies, and systematic reviews published from April 1, 2014 for PMR, and January 1, 2018 for LVV, to 31 December, 2024. Results Forty-one studies were included, all of which were observational. Fast-track clinics for suspected PMR shortened the time to diagnosis (80-53 days and 12-7 days, 2 studies, P = .001) and hospitalisations (20%-3.5%, P = .001). PMR-like symptoms with covert LVV at imaging were associated with a higher relapse risk compared with isolated PMR (odds ratio: 6.99, 95% CI: 2.30-21.74) and required more glucocorticoids (prednisone equivalents dose at 12 months 7.5 ± 13.5 mg/d vs 2.4 ± 3.4 mg/d, P = .016) and disease-modifying antirheumatic drugs (conventional synthetic 50% vs 13%, P = .001; biological 28% vs 2%, P = .001). Multimodal diagnostic approaches integrating clinical and laboratory assessment, imaging, and/or temporal artery biopsy accurately diagnosed GCA (sensitivity 92%-99%, negative predictive value 85%-99%). No evidence emerged concerning TAK referral and diagnosis. Conclusions Initial evidence on fast-track clinics emerged in PMR. Subclinical LVV with PMR-like presentation is increasingly recognised, but its long-term prognosis remains unclear. The value of multimodal diagnostic approaches has been shown in GCA; studies are lacking in TAK and PMR.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a frequently relapsing systemic autoimmune disorder characterized by inflammation and destruction of small- to medium-sized blood vessels resulting in potentially life-threatening organ damage. Of the three AAV subtypes, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are the most common. The aims of treatment are to rapidly control active disease with induction therapy [typically rituximab (RTX) (the new standard-of-care) or cyclophosphamide alongside glucocorticoids (GC) and avacopan], followed by less aggressive maintenance strategies to reduce the risk of relapse. International and national guidelines for the treatment of GPA/MPA are generally aligned, with all guidelines highlighting a need to reduce treatment-related adverse events through rapid GC tapering and the use of GC-sparing avacopan treatment. Guidelines will continue to evolve as ongoing studies provide new insights into alternative (GC-sparing) treatment options and optimal RTX-based treatment regimens.

OBJECTIVE:Eosinophilic granulomatosis with polyangiitis (EGPA) is a small vessel vasculitis characterized by eosinophilia, asthma, and ear, nose, and throat (ENT) involvement. Although glucocorticoids (GCs) are effective in controlling symptoms, relapses and GC dependence are common. The aim of this study was to develop predictive models for vasculitis relapse and GC-dependent asthma and/or ENT symptoms. METHODS:This multicenter European retrospective cohort study included patients with EGPA fulfilling the 2022 American College of Rheumatology/EULAR criteria. Using Fine-Gray and logistic regression, we developed two multivariable prediction models, one for vasculitis relapse and another for GC-dependent asthma and/or ENT symptoms at 2 Internal validation was performed using bootstrapping. RESULTS:A total of 809 patients were observed for a median of 72 months (interquartile range 37-115). Vasculitis relapse occurred in 228 patients with a 12-year cumulative incidence of 41.2% (95% confidence interval 36.3-46.8). GC-dependent asthma and/or ENT symptoms were observed in 66.4% at two years. Predictors of vasculitis relapse included age (nonlinear), GC-dependent asthma before EGPA diagnosis (hazard ratio [HR] 1.57), arthralgia (HR 1.27), myocarditis (HR 1.74), peripheral neuropathy (HR 1.39), myeloperoxidase-antineutrophil cytoplasmic antibody (HR 1.56), and baseline eosinophil count (nonlinear). Predictors of GC-dependent asthma and/or ENT symptoms included older age (odds ratio [OR] 0.98 per year), GC-dependent asthma at diagnosis (OR 1.50), chronic sinusitis (OR 1.78), and baseline eosinophil count (OR 0.70 per 109/L). CONCLUSION:Using a large cohort with EGPA, we developed predictive models for vasculitis relapse and GC-dependent asthma and/or ENT symptoms. These tools may help guide treatment decisions. Prospective external validation in the current therapeutic era is warranted.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare and potentially life-threatening systemic, inflammatory disease with multi-organ manifestations, variable presentation and complex pathology. Multiple interconnected immunological pathways are implicated in EGPA pathology, including a type-2 immune response driving predominantly eosinophilic inflammation, B-cell mediated autoimmunity, neutrophil activation, and the generation of pathogenic anti-neutrophil cytoplasmic antibodies, all of which can contribute to tissue/organ damage. High-dose glucocorticoids are the mainstay treatment for EGPA, but over the past two decades the development of biologic treatments targeting interleukin (IL)-5, eosinophils and B-cells has revitalized the treatment landscape. Mepolizumab, a humanized monoclonal antibody that specifically targets IL-5, and benralizumab, which targets the IL-5 receptor (IL-5Rα), are both approved for the treatment of patients with non-severe relapsing or refractory EGPA. In Phase III trials, these biologics have demonstrated favorable safety profiles and efficacy, with treatment leading to remission induction, remission maintenance, and oral glucocorticoid sparing benefits. However, as understanding of the full complexity of EGPA pathogenesis improves, new treatment targets are emerging. Consequently, understanding key pathogenic mechanisms at the patient level, enabling a more tailored treatment approach, is an important goal for future research.

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.

Background:Established treatments for granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) include the use of immunosuppressive agents for remission induction followed by maintenance therapy. However, patients continue to experience disease progression, organ damage, and adverse events related to current therapies. Avacopan, an oral selective C5a receptor antagonist, was approved by the European Commission in January 2022 for the treatment of adult patients with severe, active GPA or MPA in combination with rituximab (RTX) or cyclophosphamide (CYC). In the pivotal phase 3 ADVOCATE (Avacopan Development in Vasculitis to Obtain Corticosteroid Elimination and Therapeutic Efficacy) study, avacopan was noninferior to prednisone taper in achieving remission at week 26 and superior in sustaining remission at week 52; furthermore, a greater improvement in estimated glomerular filtration rate with avacopan was also observed at week 52. The AvacoStar study will generate data on the benefit and risk and safety profile of avacopan in patients in a real-world context, including in those where treatment may potentially continue beyond 1 year. Objective:The primary objective of AvacoStar is to evaluate the incidence of defined medical events of special interest in patients with antineutrophil cytoplasmic antibody-associated vasculitis commencing avacopan. These include liver injury, cardiac safety, serious infections, and malignancy. Methods:AvacoStar is a noninterventional, multinational, prospective postauthorization safety study. It will enroll up to 500 patients in Germany and the United Kingdom in 2 groups of approximately 250 participants each: those treated with avacopan (plus a standard of care at local investigators' discretion; usually an RTX- or CYC-based regimen) and a second cohort treated with a CYC- or RTX-based induction regimen without avacopan. Avacopan and the standard of care will be prescribed in the usual manner in accordance with the corresponding summary of product characteristics under the sole decision of the investigator. The treatment decision will fall within current established practice. Eligible participants will be aged ≥18 years with severe, active GPA or MPA as determined by the investigator at the time of commencing avacopan or non-avacopan standard-of-care induction therapy. Patients will be followed for up to 7 years. Results:This study has been enrolling patients since September 11, 2023. The final report is expected in the second half of 2031; interim reports are planned every 24 months after the first patient first visit. Conclusions:The AvacoStar study will be the largest European prospective real-world evidence comparative study conducted to date that evaluates the long-term safety of avacopan in severe, active GPA or MPA. This study is expected to yield important insights on the use of avacopan in severe, active GPA or MPA in a real-world setting.

Evidence is limited on the clinical and economic burden of eosinophilic granulomatosis with polyangiitis (EGPA) in Europe. We evaluated EGPA healthcare resource utilisation (HCRU), days off work, and costs in Germany. This analysis used claims data from the German statutory health insurance fund AOK Plus. Patients with newly diagnosed EGPA (index date 2016–2020; ≥ 12 months pre-diagnosis health plan enrolment) were matched (1:4) with general insured individuals without EGPA. Baseline was 12 months pre-diagnosis; follow-up was until 31 December 2020, insurance disenrollment, or death. Outcomes included HCRU and related costs and days off work. The study included 155 patients and 620 matched individuals. In the EGPA cohort, all-cause HCRU was higher post-diagnosis than during baseline in all categories. Mean annualised in-patient hospitalisations/patient and pharmacy claims/patient for any EGPA therapy were 2.99 and 5.87, respectively, during 1-year post-diagnosis versus 1.15 and 1.80, respectively, during baseline. Mean total annualised cost of all-cause HCRU/patient with EGPA was €19,700 during 1-year post-diagnosis versus €6,678 during baseline, with in-patient hospitalisations and pharmacy costs the main cost drivers of EGPA care. Over 5 years post-diagnosis, mean annualised HCRU rate per patient was significantly higher for the EGPA versus the matched cohort for all evaluated aspects of HCRU (p < 0.001). The mean total annualised all-cause HCRU cost was sevenfold higher (EGPA €14,771/patient vs matched cohort €2,094/patient; p < 0.001). In-patient hospitalisation (€8,276/patient) was the single largest driver of all-cause costs over 5 years post-diagnosis. Mean total days off work and associated annualised costs of productivity loss were also significantly higher over 5 years post-diagnosis in the EGPA versus the matched cohort (30.74 vs 13.35 days/year; €3,632 vs €1,555 annually/patient, both p < 0.001). These real-world data highlight the substantial economic burden associated with EGPA, characterised by increased HCRU, costs and productivity losses, underscoring the need for effective management strategies.

Rationale: The 1-year double-blind period of the MANDARA trial (NCT04157348) demonstrated non-inferiority of benralizumab to mepolizumab for achieving remission, in adults with relapsing/refractory eosinophilic granulomatosis with polyangiitis (EGPA). Here, we report the 2-year combined double-blind and ongoing open-label extension (OLE) data. Methods: On completion of the double-blind period (n=136/140) comparing benralizumab 1x30mg versus mepolizumab 3x100mg subcutaneously every 4 weeks, patients were invited to enter the OLE where they continued benralizumab (benra/benra) or switched from mepolizumab to benralizumab (mepo/benra). Endpoints included remission (Birmingham Vasculitis Activity Score=0 and oral glucocorticoid [OGC[ dose ≤4 mg/day), OGC use, relapse, blood eosinophil count (bEOS), Asthma Control Questionnaire (ACQ-6), pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1), and safety. Results: In total, 128 patients entered the OLE (n=66 benra/benra, n=62 mepo/benra; mean age 52.8 years; 60.2% female), and 119 completed OLE Year 1. Baseline characteristics of those entering the OLE were similar to the double-blind period. At Week 104, over 60% in both groups (41 [62.1%] benra/benra and 42 [67.7%] mepo/benra patients) achieved remission. During the OLE, 51 (77.3%) benra/benra and 42 (67.7%) mepo/benra patients had no relapses. The percentage of benra/benra patients who discontinued OGCs was similar at Weeks 49-52 (27 [40.9%]) and Weeks 101-104 (29 [43.9%]), while the percentage increased for mepo/benra patients between Weeks 49-52 (16 [25.8%]) and Weeks 101-104 (27 [43.5%]; Figure). The median (IQR) OGC dose at Weeks 101-104 was 0.5 (0,5) in benra/benra and 1.36 (0,5) mg/day in mepo/benra patients. The median (IQR) bEOS in benra/benra patients was 20 (10,40) cells/µL at both Weeks 52 and 100; bEOS were depleted in mepo/benra patients from 70 (40,90) cells/µL to 20 (10,50) cells/µL by 4 weeks after switching. Mean (SD) ACQ-6 scores were 0.64 (0.78) in benra/benra patients and 0.60 (0.76) in mepo/benra patients at Week 104 compared with 1.39 (1.18) and 1.11 (0.95) at baseline. Mean (SD) pre-BD FEV1 was 2.59 (0.90) L versus 2.62 (0.84) L in benra/benra versus mepo/benra patients at Week 52, and 2.61 (0.90) versus 2.63 (0.81) L, at Week 100. Safety of mepolizumab and benralizumab was consistent with their known profiles. Conclusions: In patients with EGPA receiving benralizumab, remission rates, OGC discontinuation, and bEOS depletion were durable over 104 weeks with low relapse rates, and without loss of asthma control or lung function decline. Additional bEOS depletion and OGC sparing was observed in patients switching from mepolizumab to benralizumab.

BACKGROUND:Gastrointestinal involvement is common in eosinophilic granulomatosis with polyangiitis (EGPA) and has a poor prognosis. OBJECTIVES:The aim of our study was to determine the density of eosinophils in the gastrointestinal tract that should be considered pathological in patients with EGPA, and how clinically and prognostically relevant intramucosal eosinophil accumulation is in patients with EGPA. METHODS:Forty-nine subjects were included in the study: 18 with EGPA (9 women) and as a control group 31 with other rheumatological inflammatory diseases. Two hundred and forty-four biopsies from the gastrointestinal tract of the study participants were analyzed. RESULTS:Histologically, there was no significant difference in eosinophil counts between patients with EGPA and the control group; however, there was an increased density when macroscopic gastrointestinal inflammation was already present. CONCLUSIONS:Biopsies from macroscopically unremarkable mucosa appear to have limited diagnostic utility.

Eosinophilic granulomatosis with polyangiitis (EGPA), originally termed Churg-Strauss syndrome, represents the rarest form of antineutrophil cytoplasmic antibody-associated vasculitis. It is characterized by the presence of asthma, rhinosinusitis with or without nasal polyps, eosinophilic inflammation of the blood, and tissues and necrotizing vasculitis of small to medium-sized blood vessels. Owing to its rare, multisystemic nature with diverse symptom presentation, diagnosis is complex, requiring a multidisciplinary approach and a careful array of diagnostic and clinical assessments. Conventional therapy is composed of the use of oral glucocorticoids, which are associated with long-term adverse effects, and other immunomodulatory drugs. However, earlier diagnosis and prompt tailored treatment can improve clinical outcomes and reduce drug-related toxicity. The initiation of biologic therapies, such as those blocking IL-5 or its receptor, which have recently been approved for the treatment of non-severe relapsing EGPA, has emerged as a paradigm shift in management. An illustrative case is used to present a comprehensive representation of the diagnosis, pathophysiology, and management of EGPA.