EULAR guidelines on ANCA-associated vasculitis in the real life

Anti-neutrophil cytoplasmic antibodies-associated vasculitides (AAVs) are a heterogenous group of inflammatory diseases which primarily involve small vessels and include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). They present heterogeneous clinical manifestations, while their diagnosis and management still remain a challenge for clinicians. Nowadays, the treatment is based on two different regimens: the remission-induction treatment and the remission-maintenance treatment. The therapeutic armamentarium has grown over the years, with the aim to lessen adverse effects, improve quality of life of patients and maintain the disease under control. Biological treatments are the future: they act on different pathogenic pathways and may offer in the future a personalized management approach tailored to actual clinical manifestations. The latest guidelines were published in 2015 by the European League Against Rheumatism (EULAR) and still represent the vade mecum for the management of AAVs. In this review, we will focus on the principal strategies to treatAAVs. We discuss the remission-induction therapy and the remission-maintenance therapy; we have also distinguished the management of GPA and MPA from that of EGPA, because of their different clinical picture

The management of large vessel vasculitides

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) represent the most common large vessel vasculitides (LVV). An early recognition of these conditions is crucial in order to start a prompt treatment to prevent severe ischemic complications, such as irreversible visual loss in GCA and cardiovascular or cerebrovascular accidents in TAK. Isolated glucocorticoids (GCs) still remain the cornerstone of GCA therapy. However, long-term treatment with GCs is burdened by an important toxicity. Furthermore, relapses are frequent during the follow-up period and relapsing patients have to cope with a longer duration of the GC therapy and a higher cumulative GC dose. On the other hand, TAK treatment usually relies on immunosuppressors in addition to GCs from the beginning. Also, since TAK patients are in general young women with a progressive disease, it is essential to treat this vasculitis with steroidsparing drugs in order to avoid excessive GC exposure. For this reason, efforts have been made to discover new therapeutic options able to reduce the cumulative GC dose that is strictly related to GC-toxicity. In recent years, new advances in the management of LVV have become available and have changed the therapeutic approach to these diseases. The aim of this review is to report new evidence of treatment efficacy and safety in LVV

Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study.

OBJECTIVE: Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real-life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort. METHODS: We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015-2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations. RESULTS: Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty-five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty-two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44). CONCLUSION: Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

Acute pneumonitis or vasculitis? A severe case with multiple organ involvement

This report describes a case of a 37-year-old man affected by weakness, cough, fever and arthralgia for three months and a single episode of arthritis affecting the left ankle. The symptoms worsened and he was admitted to our hospital. First level blood tests showed an increase in inflammatory proteins, leukocytosis with eosinophilia, positive anti-neutrophil cytoplasm antibody (ANCA) and PR-3 ANCA antibodies, initial renal failure with elevation of creatinine and microscopic hematuria and initial proteinuria in the urine tests. As the chest x-ray revealed a perihilar pneumonitis with a well-defined margin area in the right lung, we started antibiotic therapy. The lung was studied with high-resolution chest computed tomography, which showed interstitial lung disease with more consolidative areas, some of which had a reverse halo sign. As clinical and laboratory data suggested a multiple organ involvement, second level tests were performed to look for the presence of systemic vasculitis