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

Investigation of the Defatted Colostrum 1H-NMR Metabolomics Profile of Gilts and Multiparous Sows and Its Relationship with Litter Performance

The aim of the study was to characterize the soluble metabolomics profile of defatted colostrum of sows at different parity number (PA) and to correlate the metabolomics profile with the Brix percentage estimate of colostrum immunoglobulin G (IgG) and sow productive traits. A total of 96 Meidam (crossbreed Large White 7 Meishan) sows of PA from 1-4 (PA1: 28; PA2:26; PA3:12; PA4:26) were included, and their productive traits were recorded at 10 days post-farrowing. Colostrum IgG was quantified using a Brix refractometer, and metabolomics profile was assessed using 1H-NMR spectroscopy. Sows' PA slightly influenced the metabolomics profile of colostrum. lactose and glycine were higher in PA1 compared with PA4 (p 0.05) and N-acetylglucosamine (GlcNAc) tended to be higher in PA2 than PA3 and PA4 (p < 0.10). The Brix percentage of IgG was negatively associated with lactose and positively with creatine, myo-inositol, and O-phosphocholine (p < 0.05). Taurine was positively related to litter weight at birth. GlcNAc and myo-inositol were linked to piglet mortality at day 10 with a negative and positive trend, respectively. In conclusion, colostrum of gilts and multiparous sows had a similar metabolomics profile. Specific metabolites contributed to explanation of the variability in colostrum Brix percentage estimate of IgG concentration and the sows' productive performance

One-year clinical experience on the use of Nintedanib in Systemic Sclerosis

AIM- Systemic Sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, immune activation and fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is one of the most common causes of death. In 2019 Nintedanib was approved for SSc-related ILD, due to randomized clinical trials (RCTs) demonstrating a reduction in the annual rate of decline in Forced Vital Capacity (FVC). METHODS We reviewed eleven patients with SSc-related ILD from January 2020 to January 2021 and who started Nintedanib 150 mg twice a day. RESULTS- Non-Specific Interstitial Pneumonia (NSIP) was the most frequent HRCT pattern, followed by Usual Interstitial Pneumonia (UIP) and UIP/NSIP pattern. The mean of Modified Rodnan Skin Score (mRSS) at baseline was 9.23 (±10SD) points without any significant improvement during the follow-up. Patients continued their ongoing therapy for lung involvement. Mean FVC was 2233.6 ml [+/- 1066 ml] (61.3% predicted) at beginning and remained stable during the follow-up period. The mean modified British Council Medical Questionnaire (mmRC) decreased from 3 at baseline to 2.5 at the end of follow up and the mean of the Borg scale of dyspnea ameliorated from 7.27 at baseline to 6 at twelve months. Both the differences were not significant. Two patients stop therapy: one for partial intestinal obstruction and one for incoercible diarrhea. CONCLUSION- Nintedanib was generally well tolerated and we did not record any serious adverse even

Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study

Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA)

Adalimumab and ABP 501 in the Treatment of a Large Cohort of Patients with Inflammatory Arthritis: A Real Life Retrospective Analysis

The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive

Multidisciplinary Management of Spondyloarthritis-Related Immune-Mediated Inflammatory Disease

Immune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis and uveitis

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia, A double-blind, randomised, placebo-controlled trial

Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. Methods: In this multicenter, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with Covid-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need of supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. Results: Overall, 112 of 151 (75.4%) patients in the pulse methylprednisolone arm and 111 of 150 (75.2%) in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups [15 days (95% confidence interval (CI), 13.0 to 17.0) and 16 days (95%CI, 13.8 to 18.2); hazard ratio (HR), 0.92; 95% CI 0.71-1.20; p=0.528]. No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to Intensive Care Unit with orotracheal intubation or death (20.0% versus 16.1%; HR, 1.26; 95%CI, 0.74-2.16; p=0.176), or overall mortality (10.0% versus 12.2%; HR, 0.83; 95%CI, 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. Conclusions: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia. Message of the study: Pulse glucocorticoid therapy is used for severe and/or life threatening immuno-inflammatory diseases. The addition of pulse glucocorticoid therapy to the standard low dose of dexamethasone scheme was not of benefit in patients with COVID-19 pneumonia

Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study (2023-02-07)

Background: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. Methods: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann–Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. Results: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804–0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883–0.939; p < 0.01). Conclusions: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA

Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients