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Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Background: Major improvements in the management of rheumatoid arthritis (RA) have made clinical remission an achievable and desirable goal but, despite the relevance gained by a profound disease suppression, many patients with RA still miss clinical remission due to several factors influencing disease activity, including treatment adherence. Objective: To evaluate the effect of adherence to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on the achievement of clinical remission in a cohort of patients with new-onset inflammatory arthritis. Study design: A prospective cohort study was conducted using the ELECTRA database, which consists of clinical data from patients followed at the IRCCS Policlinico San Matteo Foundation (Pavia, Italy), linked to regional administrative healthcare databases. Methods: We enrolled patients with new-onset active disease between January 2006 and December 2013 and followed them until their first clinical remission or end of follow-up (December 2015). To assess the association of csDMARD adherence with clinical remission, we estimated the csDMARD proportion of days covered (PDC) during follow-up. PDC was added to the main clinical adjustment covariates as a time-dependent variable in a proportional hazard Cox regression model. Results: The cohort included 324 patients with a mean (SD) age of 58 (13.9) and predominantly female (74.5%). A total of 219 patients (67.6%) achieved clinical remission during follow-up and 85 (26.2%) in the first 6 months (early clinical remission). Cox regression models showed that a 10% increment of PDC increased the probability of achieving clinical remission by 10% (p < 0.001) and the probability of early clinical remission by 21% (p = 0.03). Conclusion: Patients at disease onset with higher adherence to csDMARDs were more likely to achieve clinical remission and early clinical remission. Our study highlighted the importance of close monitoring of patients to increase their likelih

Background: The assessment of giant cell arteritis (GCA) in fast‐track assessment clinics (FTA) including the use of ultrasound (US) is becoming the preferred practice in specialized centers. Methods: Patients with suspected GCA referred to the FTA of the Rheumatology Department, University of Pavia, Italy, between 2016 and 2021 were included to analyze the clinical and US findings. Results: A total of 553 US examinations were performed on 347 patients. A total of 246 were female (71%), and the mean age was 73 ± 12. Of these, 287 US on newly referred patients led to a confirmed diagnosis of GCA in 111 (39%). The sensitivity of US was 81.98% (95% CI 73.55– 88.63%), and the specificity 99.43% (95% CI 96.88–99.99%). Only 4 patients required temporal artery biopsy. The most specific symptoms to inform the pre‐test probability of GCA and differentiate from patients with other conditions were: jaw or tongue claudication, scalp tenderness, and bilateral visual loss. Headache was not reported in 33% of patients. Systemic symptoms were significantly more frequent in GCA (42.3%), together with combinations of cranial, systemic, and/or polymyalgia rheumatica symptoms. Out of 88 patients, there were 52% with a confirmed relapse. Of these, 67% had a positive US. Conclusion: The use of FTA in clinical practice ensures an early diagnosis, avoiding invasive procedures for the patient. Our data support the increasingly recognized adjunctive role of US in the monitoring of GCA.

Objective The aim of this study was to assess the real-life adherence of Italian rheumatologist to the 2013 EULAR recommendations and treatment outcome in rheumatoid arthritis (RA) patients who started a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Methods The MITRA study is an Italian multicentre observational cohort focused on treatment naïve RA patients with early diagnosis recruited in an 18-month period starting from 2015. The data related to treatment with csDMARDs during the following 12 months follow-up were presented in this paper. Results Two-hundred and fifty-nine RA patients from MITRA cohort who had a follow-up visit and started a csDMARD were included in the prospective analysis. Methotrexate was started as first conventional DMARD in 224 (86.4%) patients. During the first year after starting conventional DMARDs, 175 (67.6%) RA patients reached the pre-specified target, which was DAS28 remission (<2.6) for 112 (43.2%) patients and LDA (<3.2) for 63 (24.3%) patients. Factors that negatively impacted the target achievement were fibromyalgia (HR: 0.2 [0.05-0.81]), HAQ-DI (HR: 0.72 [0.56-0.93]) and ESR (HR: 0.99 [0.99-1]). Globally, 33 (12.7%) patients started a biologic DMARD, while 61 out of 84 (72.6%) patients who had never reached the target remained on conventional DMARD. One-hundred and ninety-three adverse events (AEs) were recorded, the majority classified as mild (91 cases, 51%). Conclusion A high proportion of RA patients achieved the target during the first-year follow-up. However, a considerable portion of RA patients did not start a biological drug although the target was never reached. AEs remain frequent with conventional DMARDs, but the majority were mild.

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

Background: While low-dose oral glucocorticoids (GCs) are recommended in the management of early arthritis, their impact on mortality is unclear. The aim of this study is to evaluate the effect of GCs on mortality in patients with early arthritis, by linking clinical and administrative databases. Methods: The study included patients with new-onset rheumatoid arthritis (RA) or undifferentiated arthritis (2005–2010), who received DMARDs (MTX in RA or UA with poor prognosis, hydroxychloroquine in UA) and were alive at the second year of follow-up. Low-dose GCs could be prescribed. Clinical and administrative data were linked from Administrative Health Databases (AHD) of the corresponding province, which provided us with information on drug delivery, comorbidities, hospitalization, and mortality. The effect of GCs in the first year was defined using a dichotomous variable or a 3-level categorization (not delivered, ≤7.5 mg/day, or >7.5 mg/day of prednisone) on all-cause mortality, assessed with Cox regression, either crude or adjusted for age, gender, Charlson Comorbidity Index (CCI) or single comorbidities, ACPA, HAQ, and MTX in the first year. A secondary analysis of the effect of GCs on related hospitalizations (for cardiovascular events, diabetes, serious infections, osteoporotic fractures) was also carried. Results: Four hundred forty-nine patients were enrolled (mean age 58.59, RA 65.03%) of which 51 (11.36%) died during the study. The median (IQR) follow-up was equal to 103.91 (88.03–126.71) months. Treatments with GCs were formally prescribed to 198 patients (44.10%) at ≤7.5 mg/day, although by the end of the study such treatments were received by 257 patients (57.24%); 88 patients (19.6%) were treated with GCs at >7.5 mg/day. In adjusted analyses, the GC delivery (HR, 95% CI 1.35 (0.74, 2.47)) did not significantly predict mortality — both at a low (HR, 95% CI 1.41 (0.73, 2.71)) and at a high (HR, 95% CI 1.23 (0.52, 2.92)) dosage. When “all-cause hospital

Objective To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods We conducted a multicentre, international, retrospective cohort study. Results 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusion The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Objectives: To analyse the effectiveness, safety and steroid-sparing effect of AZA and MTX as induction of remission and maintenance treatment in eosinophilic granulomatosis with polyangiitis. Methods: We retrospectively collected data from 57 patients divided into four groups according to treatment: MTX/AZA as first-line agents (MTX1/AZA1) in non-severe disease or as second-line maintenance therapy (MTX2/AZA2) in severe disease previously treated with CYC/rituximab. During the first 5 years of treatment with AZA/MTX we compared the groups according to: remission rate [defined as R1: BVAS 1⁄4 0; R2: BVAS 1⁄4 0 with prednisone ≤5 mg/day; R3 (MIRRA definition): BVAS 1⁄4 0 with prednisone ≤3.75 mg/day], persistence on therapy, cumulative glucocorticoid (GC) dose, relapse and adverse events (AEs). Results: There were no significant differences in remission rates (R1) in each group (63% in MTX1 vs 75% in AZA1, P 1⁄4 0.53; 91% in MTX2 vs 71% in AZA2, P 1⁄4 0.23). MTX1 allowed R2 more frequently in the first 6 months compared with AZA1 (54% vs 12%, P 1⁄4 0.04); no patients receiving AZA1 achieved R3 up to the first 18 months (vs 35% in MTX1, P 1⁄4 0.07). The cumulative GC dose was lower for MTX2 vs AZA2 (6 g vs 10.7 g at 5 years, P 1⁄4 0.03). MTX caused more AEs compared with AZA (66% vs 30%, P 1⁄4 0.004), without affecting the suspension rate. No differences emerged in time-to-first relapse, although fewer patients treated with AZA2 had asthma/ENT relapses (23% vs 64%, P 1⁄4 0.04). Conclusion: A significant proportion of patients achieved remission with both MTX and AZA. MTX1 had an earlier remission on a lower GC dose but MTX2 had a better steroid-sparing effect.

Background: Human immunodeficiency virus (HIV) has a protean clinical picture, in rare instances manifesting as systemic autoimmune disorders such as vasculitides. HIV-induced autoimmune diseases often do not respond well to systemic immunosuppressive therapy. Opportunistic infections may occur in patients with either acquired immunodeficiency syndrome (AIDS) or heavy immunosuppressive treatment, and can further complicate the clinical presentation. Case presentation: A patient presenting with immunoglobulin A (IgA) vasculitis (IgAV) with treatment-refractory purpuric skin rash and suspect intestinal vasculitis was discovered to have AIDS. HIV was the trigger of IgAV, and cytomegalovirus (CMV) colitis mimicked intestinal vasculitis. Antiretroviral treatment improved both CMV colitis and the control of the autoimmune disease. Conclusions: An autoimmune disease relapsing despite adequate immunosuppressive treatment and/or the presence of recurrent severe opportunistic infections may be clues to an underlying HIV infection.

Objectives. To analyse humoral and cellular immune response to mRNA COVID-19 vaccines in patients with GCA. Methods. Consecutive patients with a diagnosis of GCA receiving two doses of BNT162b2 vaccine were assessed at baseline and 3 weeks from the second vaccine dose. Healthy subjects (n 1⁄4 51) were included as controls (HC). Humoral response was assessed with Spike-specific IgG antibody response (S-IgG) and neutralizing antibodies (NtAb). Specific T cell response was assessed by enzyme linked immunosorbent spot (ELISpot). Results. Of 56 included patients with GCA, 44 were eligible after exclusion of previous evidence of COVID-19 and incomplete follow-up. A significant proportion of patients with GCA (91%) demonstrated antibody (S-IgG) response, but this was significantly lower than HCs (100%); P < 0.0001. Neutralizing activity was not detected in 16% of patients with GCA. Antibody titres (S-IgG and NtAb) were significantly lower compared with HCs. Humoral response (S-IgG and NtAb) was significantly hampered by treatment with MTX. Cellular response was lacking in 30% of patients with GCA (vs 0% in HCs; P < 0.0001). Cellular response was significantly influenced by the levels of baseline peripheral T-lymphocytes and by glucocorticoid treatment. Treatment with tocilizumab did not affect any level of the immune response elicited by vaccination. Conclusions. Although patients with GCA apparently achieve a robust antibody seroconversion, there is a significant impairment of the neutralizing activity. MTX significantly reduced all levels of the humoral response. Up to one-third of patients do not develop a cellular immune protection in response to COVID-19 vaccination.

Objective: To assess the prevalence and impact on damage accrual of different levels of disease activity in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Methods: Patients with GPA and MPA followed for ≥5 years in 2 different centers were included. Disease activity and damage were assessed using the Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI), respectively. Three levels of remission were defined: complete remission (BVAS = 0, negative for antineutrophil cytoplasmic antibody [ANCA], off treatment), clinical remission off therapy (CROffT; BVAS = 0, positive for ANCA), and clinical remission on therapy (CROnT; BVAS = 0, negative or positive for ANCA, glucocorticoids ≤5 mg/day and/or immunosuppressant). A low disease activity state (LDAS) was defined as 0 < BVAS ≤3, low-dose glucocorticoids (≤7.5 mg/day), and/or immunosuppressant. Remission or LDAS were defined as prolonged when lasting ≥2 consecutive years. Results: A total of 167 patients were included: 128 (76.6%) with GPA, 39 (23.4%) with MPA, mean ± SD age 51.0 ± 16.7 years. During a 5-year follow-up, 10 patients (6.0%) achieved prolonged complete remission, 6 (3.6%) prolonged CROffT, 89 (53.3%) prolonged CROnT, 42 (25.1%) prolonged LDAS, and 20 (12.0%) never achieved LDAS. The VDI score at 5 years progressively worsened according to increasing levels of disease activity targets (complete remission, CROffT, CROnT, and LDAS). The mean ± SD 5-year VDI score was higher in patients not achieving prolonged remission compared to those who did (3.7 ± 2.0 versus 2.2 ± 1.9; P < 0.0001). By multivariate analysis, baseline ear, nose, and throat (P = 0.006), and lung involvement (P = 0.047) were negative predictors of prolonged remission. Conclusion: More than 60% of patients with GPA/MPA achieved prolonged remission, which was associated with better long-term outcomes. In contrast, prolonged LDAS correlated with increased damage accrual and was

Objective: Early diagnosis and tight control improve outcomes of rheumatoid arthritis (RA). However, whether establishing an early arthritis clinic (EAC) is sustainable for national health systems is not known. This analysis aimed to compare effectiveness and costs of an EAC compared to patients followed by the current standard of care. Methods: A retrospective study on administrative health databases of patients with a new diagnosis of RA was conducted: 430 patients followed in an EAC were enrolled, and 4 non-EAC controls were randomly matched for each. During 2 years of follow-up, the mean health care costs (outpatient, inpatient, pharmaceutical, and global) and 3 effectiveness measures (number and length of hospitalization and quality of care) of the EAC and non-EAC were estimated. The incremental cost-effectiveness ratio was calculated as well as the cost-effectiveness acceptability curve. Results: The cohorts included patients with a mean age of 55.4 years, and 1,506 patients (70%) were female. The mean pharmaceutical (2,602 versus 1,945 euros) and outpatient (2,447 versus 1,778 euros) costs were higher in the EAC cohort. Conversely, a higher rate of non-EAC patients had a low adherence to quality-of-care indicators. The expected number of hospitalizations and the length of stay were statistically significantly higher in the non-EAC versus EAC. Conclusion: Despite an expected increase in outpatient costs (visits and diagnostic tests) and pharmaceutical costs, the reduction in terms of number and length of hospitalizations and the higher adherence to international quality-of-care guidelines support the effectiveness of the EAC model.

Purpose of Review: The purpose of this review is to discuss the most recent evidence on the treatment innovations and future prospective in the management of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). Recent Findings: In AAV, a growing body of research is available on novel treatment options for remission induction and to clarify some uncertainties concerning the optimal use of available drugs. Efforts are being made to reduce the toxicity associated with high-dose, prolonged glucocorticoids (GC) regimens. Despite major advances in the prognosis of AAV, relapses are still common and the intensity and duration of remission treatment constitute a great challenge in the management of these chronic conditions. Summary: A paradigm shift in practice in the management of AAV is being supported by recent evidence suggesting the comparable efficacy and improved safety profile of schemes with a reduced dose of GC for the induction and maintenance of remission in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Moreover, recent appraisal of pathogenetic mechanisms, including complement activation pathways, has introduced the revolutionary concept of an alternative to GC, such as avacopan. Plasma exchange failed to prevent end-stage renal disease and mortality in patients with severe renal involvement or pulmonary haemorrhage according to a large multicentre randomised trial. Intensified immunosuppressive strategies for patients with life-threatening manifestations, including the combination of rituximab (RTX) with cyclophosphamide (CYC) have revealed promising preliminary data. New evidence for the use of alternative immunosuppressive agents (e.g. mycophenolate mofetil or abatacept) for the induction of remission in patients with non-severe disease is emerging. Several studies have been recently published, or are ongoing, to assess the optimal strategy and duration of maintenance of remission with t