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ObjectiveTo compare long-term efficacy of remission-maintenance regimens in patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides.MethodsThe 28-month Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis trial compared rituximab with azathioprine to maintain remission in patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited ANCA-associated vasculitis. Thereafter, prospective patient follow-up lasted until month 60. The primary endpoint was the major-relapse rate at month 60. Relapse and serious adverse event-free survival were also assessed.ResultsAmong the 115 enrolled patients, only one was lost to follow-up at month 60. For the azathioprine and rituximab groups, respectively, at month 60, the major relapse-free survival rates were 49.4% (95% CI 38.0% to 64.3%) and 71.9% (95% CI 61.2% to 84.6%) (p=0.003); minor and major relapse-free survival rates were 37.2% (95% CI 26.5% to 52.2%) and 57.9% (95% CI 46.4% to 72.2%) (p=0.012); overall survival rates were 93.0% (95% CI 86.7% to 99.9%) and 100% (p=0.045) and cumulative glucocorticoid use was comparable. Quality-adjusted time without symptoms and toxicity analysis showed that rituximab-treated patients had 12.6 months more without relapse or toxicity than those given azathioprine (p<0.001). Antiproteinase-3-ANCA positivity and azathioprine arm were independently associated with higher risk of relapse. HRs of positive ANCA to predict relapse increased over time.ConclusionThe rate of sustained remission for ANCA-associated vasculitis patients, following rituximab-based or azathioprine-based maintenance regimens, remained superior over 60 months with rituximab, with better overall survival.Trial registration numberNCT00748644.

Purpose of ReviewThis review provides an update on recent advances in the diagnosis, pathogenesis, clinical presentation, histopathological findings, and treatment approaches for antineutrophil cytoplasmic antibody (ANCA) vasculitis–associated interstitial lung disease (AAV-ILD) with a focus on literature published in the last 3 years.Recent FindingsAlthough there is no validated definition of AAV-ILD, which contributes to some of the heterogeneity seen in study results, there has been an increasing number of publications in recent years on this topic. Most patients with AAV-ILD have MPO-ANCA vasculitis, and this association appears to reduce their 5-year-survival to 60–66% (Sun et al. BMC Pulm Med 21(1), 2021, Maillet et al. J Autoimmun 106, 2020). Median age of diagnosis ranges from mid-60 s to mid-70 s (Ando et al. Respir Med 107(4), 2013), Kagiyama et al. BMJ Open Respir Res 2(1):1–9, 2015, Hozumi et al. Lung 194(2):235–42, 2016, Liu et al. Chest 156(4):715–23, 2019, Maillet et al. J Autoimmun 106, 2020, Wurmann et al. Sarcoidosis Vasc Diffuse Lung Dis 37(1):37–42, 2020, Watanabe et al. BMC Pulm Med 19(1), 2019). Computed tomography (CT) chest imaging for patients with AAV-ILD often shows a usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) pattern (12–58% and 13–61%, respectively) (Sun et al. BMC Pulm Med 21(1), 2021, Maillet et al. J Autoimmun 106, 2020, Wurmann et al. Sarcoidosis Vasc Diffuse Lung Dis 37(1):37–42, 2020, Watanabe et al. BMC Pulm Med 19(1), 2019, Baqir at al. Sarcoidosis Vasc Diffuse Lung Dis Off J WASOG 36(3):195–201, 2019). Additionally, lung biopsies typically do not demonstrate active inflammation, or capillaritis, questioning whether these patients should be treated with either immunotherapy or anti-fibrotic therapy, or both (Hozumi et al. Lung 194(2):235–42, 2016, Liu et al. Chest 156(4):715–23, 2019, Kitching at al. Nat Rev Dis Prim 6(1):71, 2020, Tanaka et al. Respir Med 106(12):1765–70, 2012).SummaryBesides immunosuppressive treatments, recent advances in anti-fibrotic therapy may offer patients with progressive AAV-ILD an alternative and/or more effective and individualized treatment option.

Background Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are subgroups of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) defined historically by clinical and histological features. GPA and MPA are heterogeneous entities with overlapping phenotypes. To identify novel subgroupings, cluster analysis was used to explore the phenotypic spectrum of AAV. Methods This study used a dataset of patients newly diagnosed as having GPA and MPA enrolled in five clinical trials. One cluster model included nine clinical baseline variables as input variables, and a second cluster model additionally included ANCA specificities. The clustering process involved multiple correspondence analyses followed by hierarchical ascendant cluster analysis. The clinical relevance of the generated clusters was analysed by their summary characteristics and outcomes. Results The analyses involved data for 673 subjects: 396 (59%) with GPA and 277 (41%) with MPA. Both cluster models resulted in five partially redundant clusters of subjects, and the model including ANCA resulted in more pertinent separations. These clusters were named ‘renal AAV with proteinase 3 (PR3)-ANCA’ (40% of subjects), ‘renal AAV without PR3-ANCA’ (32%) and ‘non-renal AAV’ (12%), ‘cardiovascular AAV’ (9%) and ‘gastrointestinal AAV’ (7%). The five clusters had distinct death and relapse rates. On the basis of 4 variables, 651 subjects (97%) could be accurately allocated to 1 of the 5 classes. Conclusions This analysis suggests that AAV encompasses five classes associated with different outcomes. As compared with the traditional GPA–MPA separation, this classification system may better reflect the phenotypic spectrum of AAV.

Current standard therapy for Wegener's granulomatosis and microscopic polyangiitis combines corticosteroids and cyclophosphamide to induce remission, followed by a less toxic immunosuppressant. This prospective, open-label, multicenter trial indicated that the safety and efficacy of azathioprine and methotrexate are similar for maintenance therapy after initial remission in these two conditions. This trial indicated that the safety and efficacy of azathioprine and methotrexate are similar for maintenance therapy after initial remission in Wegener's granulomatosis and microscopic polyangiitis. Combined corticosteroid and cyclophosphamide therapy remains the standard care for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides, despite the potential risk of adverse events, particularly with the long-term use of cyclophosphamide. 1 , 2 Moreover, even after induction with daily oral or pulse intravenous cyclophosphamide therapy, relapse rates remain as high as 15% at 12 months 3 and reach 38% at 30 months. 4 A decisive step in the approach to the treatment of Wegener's granulomatosis and microscopic polyangiitis was the development of a staged induction–maintenance strategy to reduce cumulative exposure to cyclophosphamide. This strategy uses cyclophosphamide to induce remission, followed by a less toxic immunosuppressant. . . .

Objective To assess markers of neutrophil activation such as calprotectin and N-formyl methionine (fMET) in anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) and large-vessel vasculitis (LVV). Methods Levels of fMET, and calprotectin, were measured in the plasma of healthy controls ( n =30) and patients with AAV (granulomatosis with polyangiitis (GPA, n =123), microscopic polyangiitis (MPA, n =61)), and LVV (Takayasu’s arteritis (TAK, n =58), giant cell arteritis (GCA, n =68)), at times of remission or flare. Disease activity was assessed by physician global assessment. In vitro neutrophil activation assays were performed in the presence or absence of formyl peptide receptor 1 (FPR1) inhibitor cyclosporine H. Results Levels of calprotectin, and fMET were elevated in patients with vasculitis as compared to healthy individuals. Levels of fMET correlated with markers of systemic inflammation: C-reactive protein ( r =0.82, p <0.0001), and erythrocyte sedimentation rate ( r =0.235, p <0.0001). The neutrophil activation marker, calprotectin was not associated with disease activity. Circulating levels of fMET were associated with neutrophil activation ( p <0.01) and were able to induce de novo neutrophil activation via FPR1-mediated signaling. Conclusion Circulating fMET appears to propagate neutrophil activation in AAV and LVV. Inhibition of fMET-mediated FPR1 signaling could be a novel therapeutic intervention for systemic vasculitides.

Objective This study aimed to evaluate the safety of avacopan, an orally administered C5a receptor inhibitor, for the treatment of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis in addition to standard‐of‐care (SOC) treatment with glucocorticoids with cyclophosphamide or rituximab. Methods In this randomized 12‐week study, twice daily avacopan (10 mg or 30 mg) plus SOC was assessed versus SOC only in patients with newly diagnosed/relapsing ANCA‐associated vasculitis. Efficacy measurements included 50% or greater reduction in Birmingham Vasculitis Activity Score (BVAS) at day 85, rapid reduction (day 29) of BVAS to a score of 0 that was sustained through day 85, change in Vasculitis Damage Index (VDI), renal response (improvement in estimated glomerular filtration rate [eGFR], hematuria, and albuminuria), and health‐related quality of life (HRQoL). Results Forty‐two patients were randomized (n = 13 SOC, n = 13 avacopan 10 mg, and n = 16 avacopan 30 mg). Serious adverse events occurred in 15% and 17% of patients receiving SOC only and patients receiving avacopan with SOC, respectively. In the intent‐to‐treat population, BVAS response was high across arms (11 of 13 SOC, 11 of 12 avacopan 10 mg, and 12 of 15 avacopan 30 mg); increases in mean VDI were greater with SOC only than with avacopan plus SOC (0.3 versus 0.1). Avacopan 30 mg was numerically superior to placebo and avacopan 10 mg in early remission (15%, 8%, and 20% for SOC only, avacopan 10 mg, and avacopan 30 mg, respectively), improved eGFR (+2.0 ml/min/1.73m2, +1.3 ml/min/1.73m2, and +6.2 ml/min/1.73m2, respectively), renal response (17%, 40%, and 63%, respectively), and measures of HRQoL. Conclusion Avacopan in addition to SOC for ANCA‐associated vasculitis was well tolerated, and at the higher study dose, it appeared to improve time to remission (ClinicalTrials.gov identifier NCT02222155).

IntroductionGiant cell arteritis (GCA) is a vision-threatening systemic vasculitis for which no universally accessible diagnostic tool exists. Optic nerve sheath diameter (ONSD), measurable via ultrasound, has emerged as a promising, non-invasive biomarker of cranial GCA. The Sonographic Assessment of the Optic Nerve Sheath in Giant Cell Arteritis (SONIC-GCA) aims to validate ONSD ultrasound as a diagnostic and monitoring tool in GCA.Methods and analysisSONIC-GCA is a prospective, multicentre study enrolling patients referred for the evaluation of suspected GCA. A total of 285 participants will undergo optic nerve sheath ultrasound and digital retinal funduscopy, followed by a standardised GCA assessment. All participants will be followed for a minimum of 6 months, at which time an external adjudication committee will confirm the diagnosis of GCA. Those diagnosed with GCA will be followed for 2 years, with repeated optic nerve sheath ultrasound and digital retinal funduscopy at months 3, 6, 12, 18, 24 and at relapse, if applicable.The primary outcome is the diagnostic accuracy of ONSD to detect GCA, which will be evaluated using receiver operating characteristic curve analysis, with adjudicated GCA status serving as the reference standard. Secondary outcomes will address several complementary domains: its value for relapse monitoring will be assessed through time-dependent Cox proportional hazards models, examining whether baseline or longitudinal ONSD predicts relapse risk; intraobserver and interobserver reliability will be determined using intraclass correlation coefficients, providing quantitative estimates of measurement reproducibility; and its association with retinal findings will be evaluated by correlating ONSD measurements with ocular imaging and clinical retinal outcomes. Together, these analyses will comprehensively determine the diagnostic, prognostic and operational utility of ONSD in GCA.Ethics and disseminationThe study has been peer-reviewed by the scientific committee and approved by the CIUSSS du Nord-de-l’Île-de-Montréal Research Ethics Board. Each participating site will obtain local ethics approval prior to enrolment. All participants will provide informed consent. Results will be disseminated through peer-reviewed publications, conference presentations and webinars.Trial registration numberNCT05749094.

Background Takayasu arteritis (TAK) is a large vessel vasculitis that rarely affects children. Data on childhood TAK are scarce. The aim of this study was to analyze the presenting features, course and outcome of children with TAK, compare efficacy of treatment regimens and identify high-risk factors for adverse outcome. Methods A single-center cohort study of consecutive children fulfilling the EULAR/PRINTO/PReS criteria for childhood TAK between 1986 and 2015 was performed. Clinical phenotypes, laboratory markers, imaging features, disease course and treatment were documented. Disease activity was assessed using the Pediatric Vasculitis Disease Activity Score at each visit. Outcome: disease flare defined as new symptoms and/or increased inflammatory markers necessitating therapy escalation and/or new angiographic lesions, or death. Analysis: logistic regression tested relevant variables for flare. Kaplan-Meier analyses compared treatment regimens. Results Twenty-seven children were included; 74% were female, median age at diagnosis was 12.4 years. Twenty-two (81%) children presented with active disease at diagnosis. Treatment regimens included corticosteroids alone (15%), corticosteroids plus methotrexate (37%), cyclophosphamide (19%), or a biologic agent (11%). Adverse outcomes were documented in 14/27 (52%) children: two (7%) died within 6 months of diagnosis, and 13 (48%) experienced disease flares. The 2-year flare-free survival was 80% with biologic treatments compared to 43% in non-biologic therapies ( p  = 0.03); at last follow-up, biologic therapies resulted in significantly higher rates of inactive disease ( p  = 0.02). No additional outcome predictor was identified. Conclusions Childhood TAK carries a high disease burden; half of the children experienced flares and 7% died. Biologic therapies were associated with better control of disease activity.

This study aimed to identify immune cell alterations in granulomatosis with polyangiitis patients in remission (rGPA) that may facilitate diagnosis and prediction of relapse. Circulating immune cells were phenotypically characterized by high-dimensional CyTOF in 59 rGPA patients and 31 healthy controls (HCs). These data together with inducible cytokine expression assays and Machine Learning (ML) methods were used to identify immunophenotypic profiles distinguishing rGPA patients from HCs and patients with higher relapse frequencies. rGPA patients exhibited multiple blood cell immunophenotypic features distinct from HCs, including lymphocytopenia, a shift toward exhausted effector T cells and increased B and innate immune cell activation. Using ML methods, we identified a combination of cell features (γδ T cell depletion, monocyte and CD177 neutrophil expansion, B cell depletion) distinguishing rGPA patients from HCs and cytokine expression profiles among patients (increased IL-8 in monocytes, decreased IL-10 in monocytes and cDC2 cells) associated with relapse frequency. Two ML-based risk scores were developed and respectively shown to accurately discriminate rGPA cases from HCs and rGPA patients with more frequent disease relapse. Our findings reveal distinct patterns of immune dysregulation in rGPA patients and demonstrate potential for ML methods to facilitate disease diagnosis and outcome prediction based on immunophenotypic data.

[This corrects the article DOI: 10.3389/fimmu.2026.1726107.].